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Summary Background The quadrivalent human papillomavirus (HPV) vaccine was shown to prevent infections and lesions related to HPV6, 11, 16, and 18 in a randomised, placebo-controlled study in men aged 16–26 years. We assessed the incidences of external genital warts related to HPV6 or 11, and external genital lesions and anal dysplasia related to HPV6, 11, 16, or 18, over 10 years of follow-up. Methods The 3-year base study was an international, multicentre, double-blind, randomised, placebo-controlled trial done at 71 sites in 18 countries. Eligible participants were heterosexual men (aged 16–23 years) or men who have sex with men (MSM; aged 16–26 years). Men who had clinically detectable anogenital warts or genital lesions at screening that were suggestive of infection with non-HPV sexually transmitted diseases, or who had a history of such findings, were excluded. Eligible participants were randomly assigned (1:1) to receive three doses of either quadrivalent HPV vaccine or placebo on day 1, month 2, and month 6, administered as a 0·5-mL injection into the deltoid muscle. The 7-year, open-label, long-term follow-up extension study was done at 46 centres in 16 countries. Participants who received one or more doses of the quadrivalent HPV vaccine in the base study were eligible for enrolment into the long-term follow-up study (early vaccination group). Placebo recipients were offered the three-dose quadrivalent HPV vaccine at the end of the base study; those who received one or more quadrivalent HPV vaccine doses were eligible for enrolment into the long-term follow-up study (catch-up vaccination group). The primary efficacy endpoints were the incidence of external genital warts related to HPV6 or 11 and the incidence of external genital lesions related to HPV6, 11, 16, or 18 in all participants and the incidence of anal intraepithelial neoplasia (including anal warts and flat lesions) or anal cancer related to HPV6, 11, 16, or 18 in MSM only. The primary efficacy analysis was done in the per-protocol population for the early vaccination group, which included participants who received all three vaccine doses, were seronegative at day 1 and PCR-negative from day 1 through month 7 of the base study for the HPV type being analysed, had no protocol violations that could affect evaluation of vaccine efficacy, and had attended at least one visit during the long-term follow-up study. For the catch-up vaccination group, efficacy was assessed in the modified intention-to-treat population, which included participants who had received at least one vaccine dose, were seronegative and PCR-negative for HPV types analysed from day 1 of the base study to the final follow-up visit before receiving the quadrivalent HPV vaccine, and had at least one long-term follow-up visit. Safety was assessed in all randomised participants who received at least one vaccine dose. This study is registered with ClinicalTrials.gov , NCT00090285 . Findings Between Aug 10, 2010, and April 3, 2017, 1803 participants were enrolled in the long-term follow-up study, of whom 936 (827 heterosexual men and 109 MSM) were included in the early vaccination group and 867 (739 heterosexual men and 128 MSM) were included in the catch-up vaccination group. Participants in the early vaccination group were followed up for a median of 9·5 years (range 0·1–11·5) after receiving the third dose of the quadrivalent HPV vaccine, and participants in the catch-up vaccination group were followed up for a median of 4·7 years (0·0–6·6) after receiving the third dose. In early vaccine group participants during long-term follow-up compared with the placebo group in the base study, the incidence per 10 000 person-years of external genital warts related to HPV6 or 11 was 0·0 (95% CI 0·0–8·7) versus 137·3 (83·9–212·1), of external genital lesions related to HPV6, 11, 16, or 18 was 0·0 (0·0–7·7) versus 140·4 (89·0–210·7), and of anal intraepithelial neoplasia or anal cancer related to HPV6, 11, 16, or 18 in MSM only was 20·5 (0·5–114·4) versus 906·2 (553·5–1399·5). Compared with during the base study (ie, before quadrivalent HPV vaccine administration), during the long-term follow-up period, participants in the catch-up vaccination group had no new reported cases of external genital warts related to HPV6 or 11 (149·6 cases per 10 000 person-years [95% CI 101·6–212·3] vs 0 cases per 10 000 person-years [0·0–13·5]) or external genital lesions related to HPV6, 11, 16, or 18 (155·1 cases per 10 000 person-years [108·0–215·7] vs 0 cases per 10 000 person-years [0·0–10·2]), and a lower incidence of anal intraepithelial neoplasia or anal cancer related to HPV6, 11, 16, or 18 (886·0 cases per 10 000 person-years [583·9–1289·1] vs 101·3 cases per 10 000 person-years [32·9–236·3]). No vaccine-related serious adverse events were reported. Interpretation The quadrivalent HPV vaccine provides durable protection against anogenital disease related to HPV6, 11, 16, and 18. The results support quadrivalent HPV vaccination in men, including catch-up vaccination. Funding Merck Sharp & Dohme.

Background BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine encoding a prefusion-stabilized, membrane-anchored severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) full-length spike protein. BNT162b2 is highly efficacious against coronavirus disease 2019 (Covid-19) and is currently approved, conditionally approved, or authorized for emergency use worldwide. At the time of initial authorization, data beyond 2 months after vaccination were unavailable. Methods In an ongoing, placebo-controlled, observer-blinded, multinational, pivotal efficacy trial, we randomly assigned 44,165 participants 16 years of age or older and 2264 participants 12 to 15 years of age to receive two 30-μg doses, at 21 days apart, of BNT162b2 or placebo. The trial end points were vaccine efficacy against laboratory-confirmed Covid-19 and safety, which were both evaluated through 6 months after vaccination. Results BNT162b2 continued to be safe and have an acceptable adverse-event profile. Few participants had adverse events leading to withdrawal from the trial. Vaccine efficacy against Covid-19 was 91.3% (95% confidence interval [CI], 89.0 to 93.2) through 6 months of follow-up among the participants without evidence of previous SARS-CoV-2 infection who could be evaluated. There was a gradual decline in vaccine efficacy. Vaccine efficacy of 86 to 100% was seen across countries and in populations with diverse ages, sexes, race or ethnic groups, and risk factors for Covid-19 among participants without evidence of previous infection with SARS-CoV-2. Vaccine efficacy against severe disease was 96.7% (95% CI, 80.3 to 99.9). In South Africa, where the SARS-CoV-2 variant of concern B.1.351 (or beta) was predominant, a vaccine efficacy of 100% (95% CI, 53.5 to 100) was observed. Conclusions Through 6 months of follow-up and despite a gradual decline in vaccine efficacy, BNT162b2 had a favorable safety profile and was highly efficacious in preventing Covid-19. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently.In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle-formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety.A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups.A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.).

Background The nine-valent human papillomavirus (9vHPV) vaccine protects against infection and disease related to HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58. The pivotal 36-month Phase III immunogenicity study of 9vHPV vaccine in 9- to 15-year-old girls and boys was extended to assess long-term immunogenicity and effectiveness through approximately 10 years after vaccination. We describe results of an interim analysis based on approximately 8 years of follow-up after vaccination. Methods Participants aged 9–15 years who received three doses of 9vHPV vaccine (at day 1, month 2, and month 6) in the base study and consented to follow-up were enrolled in the long-term follow-up study extension (N = 1272 [females, n = 971; males, n = 301]). Serum was collected at months 66 and 90 to assess antibody responses. For effectiveness analysis, genital swabs were collected (to assess HPV DNA by polymerase chain reaction [PCR]) and external genital examination was conducted (to detect external genital lesions) every 6 months starting when the participant reached 16 years of age. Cervical cytology tests were conducted annually when female participants reached 21 years of age; participants with cytological abnormalities were triaged to colposcopy based on a protocol-specified algorithm. External genital and cervical biopsies of abnormal lesions were performed, and histological diagnoses were adjudicated by a pathology panel. Specimens were tested by PCR to detect HPV DNA. Results Geometric mean titers for each 9vHPV vaccine HPV type peaked around month 7 and gradually decreased through month 90. Seropositivity rates remained >90% through month 90 for each of the 9vHPV vaccine types by HPV immunoglobulin Luminex Immunoassay. No cases of HPV6/11/16/18/31/33/45/52/58-related high-grade intraepithelial neoplasia or genital warts were observed in the per-protocol population (n = 1107) based on a maximum follow-up of 8.2 years (median 7.6 years) post-Dose 3. Incidence rates of HPV6/11/16/18/31/33/45/52/58-related 6-month persistent infection in females and males were 49.2 and 37.3 per 10,000 person-years, respectively, which were within ranges expected in vaccinated cohorts. There were no vaccine-related SAEs or deaths during the period covered by this interim analysis. Conclusions The 9vHPV vaccine provided sustained immunogenicity and durable effectiveness through approximately 7 and 8 years, respectively, following vaccination of girls and boys aged 9–15 years., Highlights • We report follow-up data up to 8 years after girls/boys received 9vHPV vaccine. • Durable effectiveness was observed through up to 8 years post-vaccination. • Sustained anti-HPV antibody responses were observed through at least 7 years.

Background: A 9-valent human papillomavirus (HPV6/11/16/18/31/33/45/52/58; 9vHPV) vaccine was developed to expand coverage of the previously developed quadrivalent (HPV6/11/16/18; qHPV) vaccine. Methods: Efficacy, immunogenicity, and safety outcomes were assessed in Latin American participants enrolled in 2 international studies of the 9vHPV vaccine, including a randomized, double-blinded, controlled with qHPV vaccine, efficacy, immunogenicity, and safety study in young women aged 16–26 years, and an immunogenicity and safety study in girls and boys aged 9–15 years. Participants (N=5312) received vaccination at Day 1, Month 2, and Month 6. Gynecological swabs were collected regularly in young women for cytological and HPV DNA testing. Serum was analyzed for HPV antibodies in all participants. Adverse events (AEs) were also monitored in all participants. Results: The 9vHPV vaccine prevented HPV 31-, 33-, 45-, 52-, and 58-related high-grade cervical, vulvar, and vaginal dysplasia with 92.3% efficacy (95% confidence interval 54.4, 99.6). Anti-HPV6, 11, 16, and 18 geometric mean titers at Month 7 were similar in the 9vHPV and qHPV vaccination groups. Anti-HPV antibody responses following vaccination were higher among girls and boys than in young women. Most (>99%) 9vHPV vaccine recipients seroconverted for all 9 HPV types at Month 7. Antibody responses to the 9 HPV types persisted over 5 years. The most common AEs were injection-site related, mostly of mild to moderate intensity. Conclusions: The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Latin American young women, girls, and boys. These data support 9vHPV vaccination programs in Latin America, a region with substantial cervical cancer burden. Keywords: Human papillomavirus, Vaccine, Cervical cancer, Persistent infection, 9vHPV

Background This study evaluated the immunogenicity and safety of a licensed meningococcal serogroup B vaccine (4CMenB) administered alone according to reduced schedules in infants or catch-up series in children. Methods In this open-label, multicentre, phase 3b study (NCT01339923), infants randomised 1:1:1 received 4CMenB: 2 + 1 doses at 3½–5–11 months or 6–8–11 months of age, 3 + 1 doses at ages 2½–3½–5–11 months. Children aged 2–10 years received 2 catch-up doses administered 2 months apart. Immune responses were measured by hSBA assays against 4 strains specific for vaccine components fHbp, NadA, PorA and NHBA. Sufficiency of immune responses was defined in groups with 2 + 1 doses schedules as a lower limit ≥70% for the 97.5% confidence interval of the percentage of infants with hSBA titres ≥4, 1 month post-dose 2 for fHbp, NadA, PorA. Adverse events were collected for 7 days post-vaccination; serious adverse events (SAEs) throughout the study. Results 754 infants and 404 children were enrolled. Post-primary vaccination, 98–100% of infants across all groups developed hSBA titres ≥4 for fHbp, NadA, PorA, and 48–77% for NHBA. Sufficiency of immune responses in infants receiving 2 + 1 schedules was demonstrated for fHbp, NadA, PorA after 2 doses of 4CMenB, as pre-specified criteria were met. Following receipt of 2 catch-up doses, 95–99% of children developed hSBA titres ≥4 for 4CMenB components. Similar safety profiles were observed across groups. A total of 45 SAEs were reported, 3 of which were related to vaccination. Conclusion Reduced infant schedules and catch-up series in children were immunogenic and safe, having the potential to widen 4CMenB vaccine coverage. Funding GlaxoSmithKline Biologicals SA.

Background The background incidence of viscerotropic- (VLD) and neurotropic-like disease (NLD) unrelated to immunization in dengue-endemic countries is currently unknown. Methods This retrospective population-based analysis estimated crude and standardized incidences of VLD and NLD in twelve hospitals in Brazil (n = 3), Mexico (n = 3), and Malaysia (n = 6) over a 1-year period before the introduction of the tetravalent dengue vaccine. Catchment areas were estimated using publicly available population census information and administrative data. The denominator population for incidence rates was calculated, and sensitivity analyses assessed the impact of important assumptions. Results Total cases adjudicated as definite VLD were 5, 57, and 56 in Brazil, Mexico, and Malaysia, respectively. Total cases adjudicated as definite NLD were 103, 29, and 26 in Brazil, Mexico, and Malaysia, respectively. Crude incidence rates of cases adjudicated as definite VLD in Brazil, Mexico, and Malaysia were 1.17, 2.60, and 1.48 per 100,000 person-years, respectively. Crude incidence rates of cases adjudicated as definite NLD in Brazil, Mexico, and Malaysia were 4.45, 1.32, and 0.69 per 100,000 person-years, respectively. Conclusions Background incidence estimates of VLD and NLD obtained in Mexico, Brazil, and Malaysia could provide context for cases occurring after the introduction of the tetravalent dengue vaccine.

A 9-valent HPV (9vHPV) vaccine has been developed to protect against HPV type 6/11/16/18/31/33/45/52/58-related infection and disease. Previous safety analyses from 7 clinical trials conducted in 9vHPV vaccine recipients 9-26 years of age, including comparisons of 9vHPV and quadrivalent HPV (qHPV) vaccines in girls and women 16-26 years of age, showed that the 9vHPV vaccine was generally well tolerated. Additional safety analyses were conducted to include the results of new clinical studies. The safety profile of the 9vHPV vaccine in prior qHPV vaccine recipients (n = 3756 from 1 randomized controlled trial and 2 open-label extension studies) and young men (n = 248 9vHPV and n = 248 qHPV vaccine recipients from 1 randomized controlled trial) was evaluated. Vaccine was administered as a 3-dose regimen (at Day 1 and Months 2 and 6), and adverse events (AEs) were monitored. The most common AEs were injection-site events (91.1% and 79.0% in prior qHPV vaccine recipients and young men, respectively), the majority of which were mild. Discontinuations due to an AE were rare (0.2% and 0.0% among prior qHPV vaccine recipients and young men, respectively). In young men, the AE profile of the 9vHPV vaccine was generally similar to that of the qHPV vaccine. Overall, the 9vHPV vaccine was generally well tolerated in prior qHPV vaccine recipients and in young men, with an AE profile generally consistent with that previously reported with the broader clinical program. ispartof: HUMAN VACCINES & IMMUNOTHERAPEUTICS vol:14 issue:2 pages:396-403 ispartof: location:United States status: published

Author(s): Mendes Lobao, William; Duarte, Fernanda Gross; Burns, Jordan Danielle; de Souza Teles Santos, Carlos Antonio; Chagas de Almeida, Maria Conceicao; Reingold, Arthur; Duarte Moreira, Edson | Abstract: BackgroundThe World Health Organization has recommended the introduction of HPV vaccines into national immunization programme (NIP), but vaccination coverage remains low worldwide. We assessed the coverage and the parental acceptance of female and male HPV vaccination in Brazil after its introduction into the NIP.MethodsWe conducted a random-digit-dial survey of parents in seven major Brazilian cities from July-2015 to October-2016. A knowledge, attitude and practices questionnaire was developed and validated by expert analysis, semantic analysis, and pre-testing.Results826 out of 2,324 (35.5%) eligible parents completed the interview. Parental acceptance of the HPV vaccine for daughters and sons 18 years of age or less was high (92% and 86%, respectively). Parents refusing vaccination were less likely to know that: HPV is sexually transmitted and causes genital warts, HPV vaccination is more beneficial before sexual debut, and HPV vaccine reactions are minor, and they were more likely to believe HPV vaccination can cause severe adverse events. Parents accepting HPV vaccine for daughters but not forsons were more likely to ignore that the vaccine is recommended for boys. Attitudes associated with HPV vaccine acceptance included: general belief in vaccines, trust in the NIP and in the HPV vaccine efficacy. Among girls eligible for HPV vaccination through the NIP, 58.4% had received a two-dose scheme and 71.1% at least one dose. "No vaccination/missed vaccination at school" was the most common reason for missed HPV vaccination in theNIP.ConclusionsOne year after introduction in the NIP, most parents surveyed in Brazil accepted HPV vaccination for their daughters and sons. Low coverage in the NIP seemed to be due to challenges in adolescent vaccine delivery and HPV vaccination barriers at health-care centers, rather than to vaccine refusal.

A 9-valent human papillomavirus (6/11/16/18/31/33/45/52/58) VLP (9vHPV) vaccine has recently been proven highly efficacious in preventing disease associated with vaccine HPV types in a pivotal Phase III study. The demonstration of lot-to-lot consistency to confirm the reliability of the manufacturing process is a regulatory requirement for vaccine licensure in the United States. A randomized trial was conducted to demonstrate that three lots of 9vHPV vaccine elicit equivalent antibody response for all 9 vaccine types. The study required thorough planning because it required success on 27 separate statistical comparisons. An innovative statistical approach was used taking into account between-lot variance for more conservative power calculations. The study demonstrated equivalence of three lots of 9vHPV vaccine for all 9 vaccine types.

Background The 9-valent HPV (9vHPV) vaccine was developed to prevent infection and disease related to 9 HPV types (HPV6/11/16/18/31/33/45/52/58) which cause approximately 90% of cervical cancers, HPV-related vulvar, vaginal and anal cancers, and genital warts worldwide. In a pivotal efficacy study, the 9vHPV vaccine prevented infection and disease due to the 9 vaccine types. Duration of protection remains to be determined. Vaccines that induce long-term protection are generally characterized by the generation of immune memory. The purpose of this report is to assess the persistence of HPV antibody response and existence of immune memory at 5 years post-vaccination. Methods A subset of subjects (N = 150) who received 3 doses of 9vHPV vaccine at day 1, month 2 and month 6 in the pivotal efficacy study continued in a study extension and received a fourth dose of 9vHPV vaccine at month 60. Serum HPV antibody levels were measured pre-dose 4 and at 7 and 28 days post-dose 4 by competitive Luminex immunoassay. Adverse events were assessed using a vaccination report card. Results HPV antibodies induced following the 3-dose series of 9vHPV vaccine in the base study persisted through month 60 with seropositivity rates ranging from 77.5% to 100%. Geometric mean titers at 1 week and 1 month post-dose 4 were 1.25–4.10 and 1.65–4.88-fold higher, respectively, than levels observed 1 month following the completion of the three-dose primary series. Seropositivity rates were >99% and 100% at 1 week and 1 month post-dose 4, respectively. The fourth dose of 9vHPV vaccine was generally well tolerated. Conclusions A three-dose regimen of the 9vHPV vaccine induced persistent HPV antibody response through 5 years post-vaccination. Administration of a fourth dose resulted in a strong anamnestic response to all 9 vaccine types. These findings suggest that the efficacy of the 9vHPV vaccine will be long lasting. Clinical Trials.gov Identifier: NCT00543543 .

BACKGROUND: In this analysis, we examine the incidence and clearance of external genital human papillomavirus (HPV) infection among heterosexual males aged 16-24 years. METHODS: A total of 1732 males aged 16-24 years old in the placebo arm of a quadrivalent HPV vaccine trial were included in this analysis. Participants were enrolled from 18 countries in Africa, the Asia-Pacific region, Europe, Latin America, and North America. Subjects underwent anogenital examinations and sampling of the penis, scrotum, and perineal/perianal regions. RESULTS: The incidence rate of any HPV DNA genotype 6, 11, 16, and/or 18 detection was 9.0 cases per 100 person-years. Rates of HPV DNA detection were highest in men from Africa. Median time to clearance of HPV genotypes 6, 11, 16, and 18 DNA was 6.1, 6.1, 7.7, and 6.2 months, respectively. Median time to clearance of persistently detected HPV 6, 11, 16, and 18 DNA was 6.7, 3.2, 9.2, and 4.7 months, respectively. CONCLUSION: The study results suggest that the acquisition of HPV 6, 11, 16, and/or 18 in males is common and that many of these so-called infections are subsequently cleared, similar to findings for women. Nevertheless, given the high rate of HPV detection among young men, HPV vaccination of males may reduce infection in men and reduce the overall burden of HPV-associated disease in the community.

OBJECTIVES: The overall safety profile of the 9-valent human papillomavirus (9vHPV) vaccine was evaluated across 7 Phase III studies, conducted in males and females (nonpregnant at entry), 9 to 26 years of age. METHODS: Vaccination was administered as a 3-dose regimen at day 1, and months 2 and 6. More than 15 000 subjects received ≥1 dose of 9vHPV vaccine. In 2 of the studies, >7000 control subjects received ≥1 dose of quadrivalent HPV (qHPV) vaccine. Serious and nonserious adverse events (AEs) and new medical conditions were recorded throughout the study. Subjects testing positive for pregnancy at day 1 were not vaccinated; those who became pregnant after day 1 were discontinued from further vaccination until resolution of the pregnancy. Pregnancies detected after study start (n = 2950) were followed to outcome. RESULTS: The most common AEs (≥5%) experienced by 9vHPV vaccine recipients were injection-site AEs (pain, swelling, erythema) and vaccine-related systemic AEs (headache, pyrexia). Injection-site AEs were more common in 9vHPV vaccine than qHPV vaccine recipients; most were mild-to-moderate in intensity. Discontinuations and vaccine-related serious AEs were rare (0.1% and CONCLUSIONS: The 9vHPV vaccine was generally well tolerated in subjects aged 9 to 26 years with an AE profile similar to that of the qHPV vaccine; injection-site AEs were more common with 9vHPV vaccine. Its additional coverage and safety profile support widespread 9vHPV vaccination.

The rate of anal cancer is increasing among both women and men, particularly men who have sex with men. Caused by infection with human papillomavirus (HPV), primarily HPV type 16 or 18, anal cancer is preceded by high-grade anal intraepithelial neoplasia (grade 2 or 3). We studied the safety and efficacy of quadrivalent HPV vaccine (qHPV) against anal intraepithelial neoplasia associated with HPV-6, 11, 16, or 18 infection in men who have sex with men.In a substudy of a larger double-blind study, we randomly assigned 602 healthy men who have sex with men, 16 to 26 years of age, to receive either qHPV or placebo. The primary efficacy objective was prevention of anal intraepithelial neoplasia or anal cancer related to infection with HPV-6, 11, 16, or 18. Efficacy analyses were performed in intention-to-treat and per-protocol efficacy populations. The rates of adverse events were documented.Efficacy of the qHPV vaccine against anal intraepithelial neoplasia associated with HPV-6, 11, 16, or 18 was 50.3% (95% confidence interval [CI], 25.7 to 67.2) in the intention-to-treat population and 77.5% (95% CI, 39.6 to 93.3) in the per-protocol efficacy population; the corresponding efficacies against anal intraepithelial neoplasia associated with HPV of any type were 25.7% (95% CI, -1.1 to 45.6) and 54.9% (95% CI, 8.4 to 79.1), respectively. Rates of anal intraepithelial neoplasia per 100 person-years were 17.5 in the placebo group and 13.0 in the vaccine group in the intention-to-treat population and 8.9 in the placebo group and 4.0 in the vaccine group in the per-protocol efficacy population. The rate of grade 2 or 3 anal intraepithelial neoplasia related to infection with HPV-6, 11, 16, or 18 was reduced by 54.2% (95% CI, 18.0 to 75.3) in the intention-to-treat population and by 74.9% (95% CI, 8.8 to 95.4) in the per-protocol efficacy population. The corresponding risks of persistent anal infection with HPV-6, 11, 16, or 18 were reduced by 59.4% (95% CI, 43.0 to 71.4) and 94.9% (95% CI, 80.4 to 99.4), respectively. No vaccine-related serious adverse events were reported.Use of the qHPV vaccine reduced the rates of anal intraepithelial neoplasia, including of grade 2 or 3, among men who have sex with men. The vaccine had a favorable safety profile and may help to reduce the risk of anal cancer. (Funded by Merck and the National Institutes of Health; ClinicalTrials.gov number, NCT00090285.).

Background. We examined the baseline prevalence of penile, scrotal, perineal/perianal, and intra-anal human papillomavirus (HPV) infection in human immunodeficiency virus (HIV)‐seronegative men who have sex with men (MSM). Methods. Data were analyzed from 602 MSM aged 16‐27 years with

Background. We examined the baseline prevalence of penile, scrotal, and perineal/perianal human papillomavirus (HPV) in heterosexual men (HM). We also evaluated baseline characteristics of HM to assess factors associated with prevalent HPV detection. Methods. We tested serum samples from 3463 HM aged 16–24 years with 1–5 lifetime female sexual partners for antibodies to HPV 6, 11, 16, and 18. We collected baseline swab specimens for the detection of DNA of HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59 from 3 areas: penile, scrotal, and perineal/perianal. Risk factors for prevalent HPV DNA detection were evaluated. Results. The prevalence of any tested HPV type was 18.7% at the penis, 13.1% at the scrotum, 7.9% at the perineal/perianal region, and 21.0% at any site. Having .3 lifetime female sexual partners had the greatest impact on HPV prevalence: odds ratio (OR) 3.2 (95% confidence interval (CI) 2.1–4.9) for HPV 6, 11, 16, and 18; and OR 4.5 (95% CI 3.3–6.1) for all HPV types tested. HPV DNA detection was highest in Africa. Neither condom usage nor circumcision was associated with HPV DNA prevalence. Conclusion. Genital-HPV DNA detection is common in young, sexually active HM. We found HPV to be most prevalent in African men and least prevalent in men from the Asia-Pacific region. Increased numbers of sexual partners was an important risk factor for HPV DNA prevalence.

To study sexual activity, the prevalence of sexual dysfunction and related help-seeking behaviors among mature adults in the United States of America, a telephone survey was conducted in 2001-2002. A total of 1491 individuals (742 men/749 women) aged 40-80 years completed the survey. Overall, 79.4% of men and 69.3% of women had engaged in sexual intercourse during the 12 months preceding the interview. Early ejaculation (26.2%) and erectile difficulties (22.5%) were the most common male sexual problems. A lack of sexual interest (33.2%) and lubrication difficulties (21.5%) were the most common female sexual problems. Less than 25% of men and women with a sexual problem had sought help for their sexual problem(s) from a health professional. Many men and women in the United States report continued sexual interest and activity into middle age and beyond. Although a number of sexual problems are highly prevalent, few people seek medical help.

Subjective sexual well-being refers to the cognitive and emotional evaluation of an individual's sexuality. This study examined subjective sexual well-being, explored its various aspects, examined predictors across different cultures, and investigated its possible associations with overall happiness and selected correlates, including sexual dysfunction. Data were drawn from the Global Study of Sexual Attitudes and Behaviors, a survey of 27,500 men and women aged 40-80 years in 29 countries. The cross-national variation of four aspects of sexual well-being (the emotional and physical satisfaction of sexual relationships, satisfaction with sexual health or function, and the importance of sex in one's life) was explored using cluster analysis, and relationships among sexual well-being, general happiness, and various correlates were examined using ordinary least squares regression and ordered logistic regression. Results from the cluster analysis identified three clusters: a gender-equal regime and two male-centered regimes. Despite this cultural variation, the predictors of subjective sexual well-being were found to be largely consistent across world regions.

Objectives To assess the importance of sex and the prevalence of sexual dysfunction among middle-aged and older adults throughout the world. Increasing life expectancy has been accompanied by improvements in the health of the middle-aged and elderly, but little is known about how this has affected their sexual experience. Methods Data were collected in 29 countries from 27,500 men and women aged 40 to 80 years using a standardized questionnaire (self-completed or by interview). Sexual dysfunction was defined as frequent and persistent problems. They included early ejaculation and erectile difficulties in men, lubrication difficulties and pain during intercourse in women, and a lack of sexual interest, an inability to achieve orgasm, and a feeling of unpleasurable sex in both. Results More than 80% of the men and 65% of the women had had sexual intercourse during the past year. Of these subjects, the most common dysfunctions were early ejaculation (14%) and erectile difficulties (10%) among the men and a lack of sexual interest (21%), inability to reach orgasm (16%), and lubrication difficulties (16%) among the women. Overall, 28% of the men and 39% of the women said that they were affected by at least one sexual dysfunction. Conclusions The results of our study indicate that sexual desire and activity are widespread among middle-aged and elderly men and women worldwide and persist into old age. The prevalence of sexual dysfunctions was quite high and tended to increase with age, especially in men. Although major between-country differences were noted, this global study revealed some clear and consistent patterns.

In Brazil, zoonotic visceral leishmaniasis (ZVL) control programs based on the mass elimination of seropositive dogs have failed to reduce the number of leishmaniasis cases. However, these programs have been done under sub-optimal conditions. We studied a cohort of dogs in an urban area in Brazil to determine, whether a dog-culling program optimized with: (i) replacement of a relatively low-sensitivity indirect immune-fluorescent test on blood eluate by a more sensitive enzyme-linked immunosorbent assay on serum blood samples; (ii) shortening of the time interval from serodiagnosis to removal of dogs; (iii) screening a high proportion of the dog population could reduce the incidence of canine Leishmania infection (CLI). The study ran from December 1997 to July 2000, with four follow-up assessments performed at approximately 8-month intervals. All dogs seropositive for anti-Leishmania antibodies were promptly eliminated. A large number of new dogs immigrated to the study area throughout the study period. They comprised 43.8-49.8% of the cohort at each follow-up assessment, and upto 15% of them already had Leishmania infection. Overall, 42 news cases of CLI were identified, for a crude incidence rate of 11.8 cases per 100 dog-years (95% CI 8.6-15.6). In the first, second, third and fourth follow-up assessments the incidence rates were 8.2 (95% CI 3.0-17.9), 12.2 (95% CI 6.3-21.2), 16.4 (95% CI 8.5-28.6) and 13.6 (95% CI 7.1-23.8), respectively. There was no statistically significant change in these rates throughout the study period. Our results suggest that dog-culling programs do not reduce the incidence of CLI, even with an optimized intervention. Possible reasons for this failure include: currently available serologic methods lack sufficient sensitivity and/or specificity to accurately identify all infected dogs warranting removal in order to prevent Leishmania transmission; destroyed dogs are immediately replaced by susceptible puppies, and quite often, by already infected dogs; and other reservoirs may be involved in maintaining canine infection. Further efforts on ZVL control should be directed to developing new strategies or to testing control methods already in place with properly designed trials.

We interviewed a population sample of 2412 men aged 40-70 y in Brazil, Italy, Japan and Malaysia about medical history, lifestyle habits and sexual behavior. Men were classified as having moderate or complete erectile dysfunction (ED) if they reported to be sometimes or never able to achieve and maintain an erection satisfactory for sexual intercourse, respectively. There were 1335 men with no diagnosis of cardiovascular or prostate diseases, diabetes, ulcer or depression, nor taking hormones. The prevalence of ED was 16.1%. ED was associated with age (the risk increased 8% per y), moderate (odds ratio (OR)=2.2) or severe (OR=4.9) lower urinary tract symptoms and smoking (OR=2.3 for >30 cigarettes/day). It was inversely associated with physical activity (OR=0.5) and higher educational levels. Between the ages of 40 and 70 y, almost one in six 'healthy' men is affected by ED. Further research should look at preclinical disease stages and genetic factors.

Objectives To estimate the incidence of erectile dysfunction (ED) in Brazilian men 40 to 69 years old at study entry during an average 2-year follow-up and study the effect of age, socioeconomic status, and medical conditions on the risk of developing ED. Methods We analyzed data from a randomly sampled cohort of men living in Salvador, Bahia (Brazil), a racially diverse city with a population of 2.3 million. A total of 602 men completed the baseline interview in 1998 and 501 completed follow-up in 2000. The analysis sample consisted of 428 (83.4%) of 513 men without ED at baseline. The men were interviewed in person, using a standardized questionnaire, and ED was assessed by a single global self-rating question. Results The crude incidence rate for ED was 65.6 cases per 1000 person-years (95% confidence interval 49.6 to 85.2). The incidence rate increased with age and was 33.3, 53.7, and 189.5 cases per 1000 person-years for men 40 to 49, 50 to 59, and 60 to 69 years old, respectively. The age-adjusted risk of developing new-onset ED was higher for men with lower education, diabetes, hypertension, and benign prostatic hyperplasia. Population projections for men 40 to 69 years old suggest that approximately 68,600 new cases of ED in Bahia and 1,025,600 in Brazil would be expected annually. Conclusions The incidence of ED in Brazilian men was 2.5-fold higher than that in the Massachusetts Male Aging Study (26/1000 person-years) and increased with age, lower education, diabetes, hypertension, and benign prostatic hyperplasia.

A small number of HPV types are related to a majority of HPV-related neoplastic lesions in humans. High-risk types such as HPV 16 and 18 are most often implicated, although other oncogenic and non-oncogenic HPV types can cause disease in men. The efficacy of the quadrivalent HPV vaccine (qHPV) against external genital lesions and intra-anal disease related to HPV in men has been demonstrated. This report examines the vaccine's efficacy against disease due to 10 additional non-vaccine HPV types, as well as efficacy regardless of HPV detection. The data presented suggest that vaccinating males against HPV 6, 11, 16 and 18 protects them against most vaccine HPV-type related anogenital disease. However, significant efficacy against disease due to non-vaccine HPV types was not seen. In addition, the data do not provide any evidence that vaccination with qHPV vaccine will increase the likelihood of disease caused by non-vaccine types in the short term.

Human papillomavirus (HPV) infection can lead to significant disease in males, including anogenital warts, intraepithelial neoplasias, and several types of oral and anogenital cancers. The quadrivalent HPV (type 6/11/16/18) L1 virus-like particle (VLP) vaccine (qHPV vaccine; Gardasil) has recently been demonstrated to prevent persistent infection and associated disease related to vaccine HPV types in males. We report the overall immunogenicity results from a trial of the quadrivalent HPV vaccine in males. Overall, 3,463 heterosexual men and 602 men who had sex with men were enrolled into a randomized, placebo-controlled, double-blind safety, immunogenicity, and efficacy study. Serum samples were collected prior to vaccination at day 1 and at months 7, 24, and 36 postvaccination. Immunogenicity was evaluated with a multiplex, competitive Luminex immunoassay. Almost all subjects (97.4 to 99.2%) seroconverted for vaccine HPV types by month 7. At month 36, 88.9%, 94.0%, 97.9%, and 57.0% of subjects were still seropositive for HPV-6, -11, -16, and -18, respectively. For all vaccine HPV types, black subjects had significantly higher antibody titers at month 7 than did both Caucasian and Asian subjects. An anamnestic antibody response was seen in men seropositive before vaccination. The vaccine was highly immunogenic in males 16 to 23 years of age; responses were comparable to those observed in women. Furthermore, the immune responses were consistent with the established efficacy of the vaccine in the prevention of incident and persistent HPV infection, anogenital warts, and anal intraepithelial neoplasia.

Prophylactic vaccination with a quadrivalent HPV (types 6, 11, 16, 18) vaccine (qHPV) has been shown to prevent infection with HPV 6/11/16/18 and associated disease in women and more recently, in men. Here we report on the safety and reactogenicity of the qHPV vaccine in males. A total of 4,065 healthy males aged 16-26 years were enrolled into a randomized, placebo-controlled, double-blind trial. Subjects were randomized 1:1 to receive qHPV vaccine or placebo at day 1, month 2, and month 6. Safety and tolerability were assessed via the collection of reported adverse experiences (AEs). All serious AEs (vaccine- or procedure-related or not) and all deaths occurring during the study were recorded. Safety analyses were conducted in all subjects who received at least one dose of vaccine or placebo. The proportion of subjects who reported at least one injection-site AE was higher in the qHPV vaccine group versus the placebo group (60.1% vs 53.7%, respectively), however most of these AEs were mild/moderate in intensity. The incidence of at least one systemic AE was comparable between the vaccine and placebo groups (31.7% vs 31.4%, respectively). There were no vaccine-related serious AEs or deaths. The occurrence of AEs did not increase with each successive injection, and among trial participants who were seropositive for at least one vaccine HPV type at enrollment, the profile of adverse events was similar to that of the entire study cohort. The qHPV vaccine was generally well tolerated in males aged 16-26 years and had a favorable safety profile.

Background Infection with human papillomavirus (HPV) and diseases caused by HPV are common in boys and men. We report on the safety of a quadrivalent vaccine (active against HPV types 6, 11, 16, and 18) and on its efficacy in preventing the development of external genital lesions and anogenital HPV infection in boys and men. Methods We enrolled 4065 healthy boys and men 16 to 26 years of age, from 18 countries in a randomized, placebo-controlled, double-blind trial. The primary efficacy objective was to show that the quadrivalent HPV vaccine reduced the incidence of external genital lesions related to HPV-6, 11, 16, or 18. Efficacy analyses were conducted in a per-protocol population, in which subjects received all three vaccinations and were negative for relevant HPV types at enrollment, and in an intention-to-treat population, in which subjects received vaccine or placebo, regardless of baseline HPV status. Results In the intention-to-treat population, 36 external genital lesions were seen in the vaccine group as compared with 89 in the placebo group, for an observed efficacy of 60.2% (95% confidence interval [CI], 40.8 to 73.8); the efficacy was 65.5% (95% CI, 45.8 to 78.6) for lesions related to HPV-6, 11, 16, or 18. In the per-protocol population, efficacy against lesions related to HPV-6, 11, 16, or 18 was 90.4% (95% CI, 69.2 to 98.1). Efficacy with respect to persistent infection with HPV-6, 11, 16, or 18 and detection of related DNA at any time was 47.8% (95% CI, 36.0 to 57.6) and 27.1% (95% CI, 16.6 to 36.3), respectively, in the intention-to-treat population and 85.6% (97.5% CI, 73.4 to 92.9) and 44.7% (95% CI, 31.5 to 55.6) in the per-protocol population. Injection-site pain was significantly more frequent among subjects receiving quadrivalent HPV vaccine than among those receiving placebo (57% vs. 51%, P

Accurate estimates of prevalence/incidence are important in understanding the true burden of male and female sexual dysfunction and in identifying risk factors for prevention efforts. This is the summary of the report by the International Consultation Committee for Sexual Medicine on Definitions/Epidemiology/Risk Factors for Sexual Dysfunction.The main aim of this article is to provide a general overview of the definitions of sexual dysfunction for men and women, the incidence and prevalence rates, and a description of the risk factors identified in large population-based studies.Literature regarding definitions, descriptive and analytical epidemiology of sexual dysfunction in men and women were selected using evidence-based criteria. For descriptive epidemiological studies, a Prins score of 10 or higher was utilized to identify population-based studies with adequately stringent criteria. This report represents the opinions of eight experts from five countries developed in a consensus process and encompassing a detailed literature review over a 2-year period.The study aims to provide state-of-the-art prevalence and incidence rates reported for each dysfunction and stratified by age and gender. Expert opinion was based on the grading of evidence-based medical literature, widespread internal committee discussion, public presentation, and debate.A wealth of information is presented on erectile dysfunction, its development through time, and its correlates. The field is still in need of more epidemiological studies on the other men's sexual dysfunction and on all women's sexual dysfunctions.A review of the currently available evidence from epidemiological studies is provided.

To study sexual activity, the prevalence of sexual dysfunction, and related help-seeking behaviour patterns among middle-aged and older people in the UK and Europe.A telephone survey was conducted using a structured questionnaire covering demographics, health, relationships, and sexual behaviour, attitudes and beliefs. In the UK, 1500 individuals completed the survey.Overall, 69% of men and 56% of women reported having sexual intercourse during the past year. The most common male sexual problems, i.e. early ejaculation (20%) and erectile dysfunction (18%), were more common in the UK than in other European regions. The most common female sexual problems, i.e. a lack of sexual interest (34%) and a lack of pleasure in sex (25%), were also more common in the UK than in other European regions. Only 26% of men and 17% of women had discussed their sexual problem(s) with a doctor.Many people in the UK maintain sexual interest and activity into middle age and beyond. Although they experience sexual problems, few seek medical help. This might be because they do not perceive such problems as serious or sufficiently upsetting, and/or are not aware of available treatments.

1. In chronic hypertension, the baroreceptors reset to hypertensive levels with a decrease in gain sensitivity, but only a few studies have evaluated baroreceptor resetting during chronic hypotension and, under these conditions, no consistent information is available concerning changes in baroreceptor gain sensitivity. Therefore, in the present study, the aortic baroreceptor function curve and the baroreflex control of heart rate (HR) were evaluated in chronic hypotension produced by myocardial infarction (MI) with no heart failure. 2. Aortic baroreceptor function curves were studied in anaesthetized three groups of rats: (i) MI-7, six rats 7 days after MI; (ii) MI-30, nine rats 30 days after MI; and (iii) five control animals (SHAM). The pressure-nerve activity relationship was measured during rapid changes in blood pressure by integrating the whole-nerve activity of the baroreceptors in a computerized beat-to-beat analysis. 3. Both long-term periods (7 or 30 days) of hypotension were accompanied by complete resetting of the baroreceptor in rats (the leftward displacement of the baroreceptor curve matched the decrease in blood pressure). Moreover, the resetting of the baroreceptor function curve was not accompanied by changes in gain sensitivity (1.47, 1.64 and 1.67%/mmHg for SHAM, MI-7 and MI-30 groups, respectively) and the baroreflex control of HR was normal comparing SHAM and MI-30 groups (bradycardic 1.62 +/- 0.18 vs 1.99 +/- 0.52 b.p.m./mmHg, respectively; tachycardic 3.6 +/- 0.5 vs 4.1 +/- 0.4 b.p.m./mmHg for, respectively). 4. The data indicate that the resetting of baroreceptors in chronic hypotension is stable and is not accompanied by changes in gain sensitivity, as observed in hypertension. This may account for the normal baroreflex control of HR observed in non-anaesthetized rats.

To study sexual activity, the prevalence of sexual difficulties and related help-seeking behaviors, among mature adults in Canada.A telephone survey (random digit dialed) was conducted in Canada in 2001 to 2002. Interviews were based on a standardized questionnaire, including demographics, general health, relationships, and sexual behaviors, attitudes and beliefs. The survey was completed by a total of 1007 individuals (500 men and 507 women) aged 40 to 80 years in Canada.Overall, 83% of men and 71% of women had engaged in sexual intercourse during the 12 months preceding the interview, and 42% of men and 36% of women engaged in sexual intercourse more than once a week. Early ejaculation (23%) and erectile difficulties (16%) were the sexual problems most frequently reported by men. The sexual problems most frequently reported by women were a lack of sexual interest (30%) and lubrication difficulties (24%). Older age (60 to 80 years compared with 40 to 49 years) and diagnoses of depression and diabetes were all significant predictors of erectile difficulties in men. More than 75% of men and women had sought no help for their sexual problem(s) from a health professional.Many middle aged and older adults in Canada report continued sexual interest and activity. Although a number of sexual problems are highly prevalent in this population, few individuals seek medical help for these problems. This may be partly because they are not sufficiently bothered by the problem or do not think that it is serious.

Although there is considerable interest in the prevalence and impact of sexual problems worldwide, to date only male erectile dysfunction has been studied systematically in Asian countries.To study the prevalence of sexual problems and associated help-seeking patterns, among mature adults in Korea and to compare the results with those obtained in other Southeast Asian and East Asian countries.As part of the Global Study of Sexual Attitudes and Behaviors (GSSAB), a survey was conducted in Korea during 2001 and 2002. Sampling was based on an intercept methodology and 1,200 individuals (600 men and 600 women) aged 40-80 years completed the survey out of 3,691 eligible subjects (response rate of 32.5%).General health, relationships, and sexual behaviors, attitudes, and beliefs.Ninety-one percent of men and 71% of women had engaged in sexual intercourse during the 12 months preceding the interview. Early ejaculation (33%) and erectile difficulties (32%) were the sexual problems most frequently reported by Korean men; these conditions were more common in Korea than in other Asian regions. Increasing age, physical inactivity, smoking, and prostate disease were significant correlates of erectile difficulties. The sexual problems most frequently reported by women in Korea were lack of sexual pleasure (37%) and inability to reach orgasm (31%). Only 2% of men and women in Korea had talked to a medical doctor about their sexual problems.Middle-aged and older adults in Korea regard sex as an important part of life and report continued sexual activity. Several sexual problems are highly prevalent in this population, but very few individuals seek medical help for these disorders. This is largely due to believing that the problem is not serious, not being bothered by the problem, difficulties regarding access to or affordability of medical care, and/or a lack of awareness of available treatments.

The Global Study of Sexual Attitudes and Behaviors was a survey of 27,500 men and women aged 40 to 80 years in 29 countries. Here we report the sexual activity, the prevalence of sexual problems and related help-seeking behaviour among subjects in Germany. A telephone survey was conducted in 2001 and 2002, using a standardised questionnaire covering demographics, general health, relationships, and sexual behaviours, attitudes and beliefs. A total of 1,500 individuals in Germany (750 men and 750 women) completed the survey. Eighty-six percent of men and 66% of women had engaged in sexual intercourse during the year preceding the interview. The most common male sexual problems were early ejaculation (15%), a lack of sexual interest, erectile dysfunction and non-pleasurable sex (each 8%). The most common female sexual problems were a lack of sexual interest (18%), non-pleasurable sex (14%) and lubrication difficulties (13%). Most sexual problems were less common among men and women in Germany than in other European regions. Increasing age was a significant predictor of a lack of sexual interest and erectile difficulties in men. Only 18% of men and 15% of women had talked to a doctor about their sexual problem(s). In conclusion, many middle-aged and older German adults reported continued sexual interest and activity. Overall, sexual problems were less prevalent in Germany compared with other European regions. Of those who experienced sexual problems, however, few had sought medical help. This was often due to a lack of perception of a problem.

The Global Study of Sexual Attitudes and Behaviors (GSSAB) is an international survey of various aspects of sex and relationships among adults aged 40-80 y. An analysis of GSSAB data was performed to estimate the prevalence and correlates of sexual problems in 13,882 women and 13,618 men from 29 countries. The overall response rate was modest; however, the estimates of prevalence of sexual problems are comparable with published values. Several factors consistently elevated the likelihood of sexual problems. Age was an important correlate of lubrication difficulties among women and of several sexual problems, including a lack of interest in sex, the inability to reach orgasm, and erectile difficulties among men. We conclude that sexual difficulties are relatively common among mature adults throughout the world. Sexual problems tend to be more associated with physical health and aging among men than women.

Despite the wealth of information on the prevalence and correlates of canine Leishmania infection (CLI), data on its incidence are still sparse, and little is known regarding risk factors for CLI. We studied a cohort of dogs in an urban area in Brazil to determine whether incidence varied with age, breed, and environmental characteristics. The mean follow-up was 1.5 years, and the crude incidence rate was 11.8 cases/100 dog-years (95% confidence interval [CI] = 8.6-15.6). In the multivariate analysis, short fur was the strongest predictor of CLI (relative risk [RR] = 9.4). In addition, our data indicate that raising pigs (RR = 4.1), chickens (RR = 3.3), or other livestock (RR = 2.6) significantly increased the risk of CLI. Thus, suggesting control measures directed towards modifying the environmental factors favoring contact between vectors, reservoirs, and susceptible humans, such as proximity to pigpens or hen houses. Furthermore, conventional control programs of insecticidal spraying of human dwellings should also apply insecticide in and around animal sheds.

Background: Depression and erectile dysfunction (ED) have a complex and bi-directional relationship. We examined the relationships between erectile dysfunction and depressive symptoms or diagnosed depression, sexual activity and sexual satisfaction. Methods: A population survey of men aged 40–70 years was carried out in Brazil, Italy, Japan and Malaysia in 1997–1998. A questionnaire was used to collect life style, sexual behaviors and medical data. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. ED was classified as moderate or complete if the men reported they were ‘‘sometimes’’ or ‘‘never’’ able to achieve and maintain an erection satisfactory for sexual intercourse. Only men with a sexual partner and not taking psychoactive drugs were considered. Results: Diagnosed depression was reported by 2.0% of the men, depressive symptoms by 21.0%. The prevalence of moderate or complete ED was 17.8%. Sexual satisfaction related to the frequency of sexual intercourse and inversely related to depressive symptoms. Depressive symptoms were positively associated with being single (odds ratio [OR] 1.7), widowed, separated or divorced (OR 2.2), moderate or complete ED (1.8), heart disease (1.6) and smoking (1.6), and negatively associated with age, physical activity and frequency of sexual intercourse. Limitations: Cross-sectional studies cannot establish a temporal cause–effect relationship. However, the confirmation of known associations reassures about the validity of the original findings. Conclusions: The findings suggest that depressive symptoms are linked to ED by the mediation of decreased sexual activity and the dissatisfaction generated by the inability to have a healthy sexual life

Objectives To measure the prevalence of erectile dysfunction (ED) in community-based populations in Brazil, Italy, Japan, and Malaysia and to study its association with the demographic characteristics, medical conditions, and health-related behavior. Methods In each country, a random sample of approximately 600 men aged 40 to 70 years was interviewed using a standardized questionnaire. All the data were self-reported. ED was assessed by the participants’ “ability to attain and maintain an erection satisfactory for sexual intercourse,” and the men were classified as not having ED if they answered “always” and as having mild, moderate, or complete ED if they answered “usually,” “sometimes,” or “never,” respectively. Results The age-adjusted prevalence of moderate or complete ED was 34% in Japan, 22% in Malaysia, 17% in Italy, and 15% in Brazil. The overall age-specific prevalence of moderate or complete ED was 9% for men aged 40 to 44 years, 12% for 45 to 49 years, 18% for 50 to 54 years, 29% for 55 to 59 years, 38% for 60 to 64 years, and 54% for those 65 to 70 years. The increased risk of ED was associated with diabetes, heart disease, lower urinary tract symptoms, heavy smoking, and depression and increased by 10% per year of age. It was inversely associated with education, physical activity, and alcohol drinking. Conclusions ED is an international problem, the prevalence and severity of which increases with age. Despite national variations in prevalence, uniform associations were found between ED and medical conditions and lifestyle habits.

CONTEXT: Recent population-based surveys suggest that the prevalence of erectile dysfunction is between 30% and 56% among men over the age of 40. Most of these studies, however, are from the United States or Europe. We need estimates of erectile dysfunction from samples of Brazilian populations, as societies that differ ethnically, culturally, and economically may also differ with respect to potential risk factors for erectile dysfunction. OBJECTIVE: To determine the prevalence of erectile dysfunction and its potential correlates. SETTING: Santos, State of São Paulo. DESIGN: Cross-sectional study. PARTICIPANTS: A population-based sample of men aged 40-70 years. Out of 718 men invited, 342 (47.6%) returned a completed questionnaire. MAIN MEASUREMENTS: Data on demographic variables, medical history, lifestyle habits and degree of erectile dysfunction. RESULTS: The prevalence of any degree of erectile dysfunction was 45.9% (minimal, 33.9%; moderate, 8.5%; complete, 3.5%) and increased with age. In bivariate age-adjusted analyses comparing men with no erectile dysfunction or minimal erectile dysfunction with those with moderate or complete erectile dysfunction, histories of diabetes or hypertension, depressive symptoms, heavy smoking and obesity were significantly associated with increased prevalence of erectile dysfunction, whereas moderate alcohol consumption was inversely associated with erectile dysfunction. In the multivariate model, age was a strong predictor of erectile dysfunction, while history of diabetes or hypertension and heavy smoking remained significantly associated with increased prevalence of erectile dysfunction. CONCLUSION: We found higher prevalence of erectile dysfunction (45.9%) among men older than 40 years old in Brazil. The variables associated with erectile dysfunction may alert physicians to patients who are at risk of erectile dysfunction as well as offer clues to the etiology of erectile dysfunction. Physicians should routinely ask their patients about sexual health and erectile dysfunction. CONTEXTO: Inquéritos populacionais recentes sugerem que a prevalência de disfunção erétil é de 30% a 56% entre homens acima de 40 anos. Entretanto, a maioria desses estudos foi realizada nos Estados Unidos ou Europa. É preciso estimar disfunção erétil a partir de amostras da população brasileira, uma vez que sociedades com diferenças étnicas, culturais e econômicas também podem diferir com respeito a fatores de risco para disfunção erétil. OBJETIVO: Este estudo visa determinar a prevalência de disfunção erétil e potenciais fatores correlatos em Santos, sudeste do Brasil. TIPO DE ESTUDO: Estudo de prevalência ou transversal. LOCAL: Cidade de Santos, Estado de São Paulo. PARTICIPANTES: Um inquérito, com questionário auto-administrado, enviado pelo correio, foi realizado numa amostra de base populacional. Monitores treinados distribuíram o questionário da pesquisa a homens de 40 a 70 anos, num envelope pré-endereçado e selado. Dos 718 homens convidados, 342 (47,6%) enviaram de volta o questionário completo. VARIÁVEIS ESTUDADAS: Os dados foram coletados por meio de questionário estruturado com informações referentes a características demográficas, história médica pregressa e hábitos de vida. O grau de disfunção erétil foi categorizado como "nenhum", "mínimo", "moderado" ou "completo" de acordo com a capacidade do indivíduo em "ter e/ou manter uma ereção satisfatória para relações sexuais". Análises bivariada ajustada para idade e multivariada foram realizadas para calcular a razão de chances (odds ratio) e intervalos de confiança de 95%. RESULTADOS: A prevalência de algum grau de disfunção erétil foi de 45,9% (mínima, 33,9%; moderada, 8,5%; completa, 3,5%), aumentando com a idade. Na análise bivariada, comparando-se os homens sem ou com disfunção erétil mínima versus aqueles com disfunção erétil moderada ou completa, história de diabetes ou hipertensão, sintomas de depressão, tabagismo (³ 40 cigarros/dia) e obesidade (índice de massa corpórea > 30,0 kg/m²) foram significativamente associados com prevalência aumentada de disfunção erétil (p < 0,05), enquanto que o consumo moderado de álcool foi inversamente associado com disfunção erétil. No modelo multivariado, idade foi um preditor forte de disfunção erétil, enquanto história de diabete ou hipertensão e tabagismo permaneceram significativamente associados com disfunção erétil. CONCLUSÃO: Consistentemente com outros estudos de prevalência de disfunção erétil, encontramos alta proporção (45,9%) de homens acima de 40 anos no Brasil com algum grau de disfunção erétil, aumentando a prevalência e a gravidade de disfunção erétil com a idade. As variáveis de estilo de vida e de condições de saúde associadas à disfunção erétil podem alertar os médicos acerca de pacientes sob risco de disfunção erétil, como também oferecem pistas quanto à etiologia da disfunção erétil. Profissionais de saúde deveriam sempre perguntar aos seus pacientes sobre saúde sexual e disfunção erétil, uma vez que uma grande proporção da população experimenta tais problemas.

OBJECTIVES: To determine the prevalence of erectile dysfunction (ED) and explore its potential sociodemographic, medical, and lifestyle correlates. METHODS: While attending the "Health Awareness Fair" in nine major cities in Brazil, 1286 men completed a questionnaire regarding ED, demographic data, and medical conditions. ED was assessed by a single global self-rating question, in which subjects were asked to describe themselves as able to achieve and maintain an erection good enough for sexual intercourse always, usually, sometimes, or never, and the responses were used to classify the subjects as having no, minimal, moderate, or complete ED, respectively. Age-adjusted bivariate and multivariate analyses were carried out to calculate the prevalence odds ratios and 95% confidence intervals for the potential covariates. RESULTS: Overall, 46.2% of men reported some degree of ED (minimal 31.5%, moderate 12.1%, complete 2.6%). The prevalence of complete ED increased 10 times from 1% to 11% between subjects younger than 40 and older than 70 years; moderate ED rose from 8% to 27%, and minimal ED remained constant at approximately 31%. In bivariate age-adjusted analyses, low educational attainment, black race/ethnicity, homo/bisexuality, and a history of diabetes, hypertension, or depression were significantly (P

Importance Infections due to Staphylococcus aureus are serious complications of cardiothoracic surgery. A novel vaccine candidate (V710) containing the highly conserved S aureus iron surface determinant B is immunogenic and generally well tolerated in volunteers. Objective To evaluate the efficacy and safety of preoperative vaccination in preventing serious postoperative S aureus infection in patients undergoing cardiothoracic surgery. Design, Setting, and Participants Double-blind, randomized, event-driven trial conducted between December 2007 and August 2011 among 8031 patients aged 18 years or older who were scheduled for full median sternotomy within 14 to 60 days of vaccination at 165 sites in 26 countries. Intervention Participants were randomly assigned to receive a single 0.5-mL intramuscular injection of either V710 vaccine, 60 μg (n = 4015), or placebo (n = 4016). Main Outcome Measures The primary efficacy end point was prevention of S aureus bacteremia and/or deep sternal wound infection (including mediastinitis) through postoperative day 90. Secondary end points included all S aureus surgical site and invasive infections through postoperative day 90. Three interim analyses with futility assessments were planned. Results The independent data monitoring committee recommended termination of the study after the second interim analysis because of safety concerns and low efficacy. At the end of the study, the V710 vaccine was not significantly more efficacious than placebo in preventing either the primary end points (22/3528 V710 vaccine recipients [2.6 per 100 person-years] vs 27/3517 placebo recipients [3.2 per 100 person-years]; relative risk, 0.81; 95% CI, 0.44-1.48; P = .58) or secondary end points despite eliciting robust antibody responses. Compared with placebo, the V710 vaccine was associated with more adverse experiences during the first 14 days after vaccination (1219/3958 vaccine recipients [30.8%; 95% CI, 29.4%-32.3%] and 866/3967 placebo recipients [21.8%; 95% CI, 20.6%-23.1%], including 797 [20.1%; 95% CI, 18.9%-21.4%] and 378 [9.5%; 95% CI, 8.6%-10.5%] with injection site reactions and 66 [1.7%; 95% CI, 1.3%-2.1%] and 51 [1.3%; 95% CI, 1.0%-1.7%] with serious adverse events, respectively) and a significantly higher rate of multiorgan failure during the entire study (31 vs 17 events; 0.9 [95% CI, 0.6-1.2] vs 0.5 [95% CI, 0.3-0.8] events per 100 person-years; P = .04). Although the overall incidence of vaccine-related serious adverse events (1 in each group) and the all-cause mortality rate (201/3958 vs 177/3967; 5.7 [95% CI, 4.9-6.5] vs 5.0 [95% CI, 4.3-5.7] deaths per 100 person-years; P = .20) were not statistically different between groups, the mortality rate in patients with staphylococcal infections was significantly higher among V710 vaccine than placebo recipients (15/73 vs 4/96; 23.0 [95% CI, 12.9-37.9] vs 4.2 [95% CI, 1.2-10.8] per 100 person-years; difference, 18.8 [95% CI, 8.0-34.1] per 100 person-years). Conclusions and Relevance Among patients undergoing cardiothoracic surgery with median sternotomy, the use of a vaccine against S aureus compared with placebo did not reduce the rate of serious postoperative S aureus infections and was associated with increased mortality among patients who developed S aureus infections. These findings do not support the use of the V710 vaccine for patients undergoing surgical interventions. Trial Registration clinicaltrials.gov Identifier: NCT00518687

Background: The Global Study of Sexual Attitudes and Behaviours was a survey of 27 500 men and women in 29 countries. Here we report the sexual activity, the prevalence of sexual difficulties and related help-seeking behaviour among participants in Australia. Methods: A telephone survey was conducted in Australia in 2001–2002, with interviews based on a standardised questionnaire. A total of 1500 individuals (750 men and 750 women) aged 40 to 80 years completed the survey. The questionnaire covered demographic information, overall health, and sexual behaviours, attitudes and beliefs. Results: Overall, 83% of men and 74% of women had engaged in sexual intercourse during the 12 months preceding the interview, and 38% of all men and 29% of all women engaged in sexual intercourse more than once a week. Early ejaculation (23%), erectile difficulties (21%) and a lack of sexual interest (18%) were the most common male sexual difficulties. The most frequently reported female sexual difficulties were: lack of sexual interest (33%), lubrication difficulties (26%) and an inability to reach orgasm (25%). Older age was a significant predictor of male erectile difficulties and of lubrication difficulties in women. Only a minority of men and women had sought help for their sexual difficulty(ies) from a health professional. Conclusions: Many middle-aged and older adults in Australia report continued sexual interest and sexual activity. Several sexual difficulties are highly prevalent in this population, but those experiencing these difficulties rarely seek medical help. This may be because they do not perceive such difficulties as serious or sufficiently upsetting.

To investigate whether Helicobacter pylori (H pylori) infection is associated with hepatitis A virus (HAV) infection, presence of enteroparasites, and other surrogates of fecal exposure.We conducted a cross-sectional study in 121 children consecutively admitted at a pediatric hospital in Salvador, Brazil. H pylori and HAV infection were identified by the presence of serum antibodies. Stool specimens were examined for the presence of ova and parasites. A structured questionnaire inquiring about sanitary conditions and life style was applied to each subject.Fifty-one of the 121 children (42.1%) were found to be seropositive for H pylori, and 45 (37.2%) for HAV. The seroprevalence of H pylori and HAV both increased significantly with age. Cross-tabulation of data showed that 26 (21.5%) were seropositive and 51 (42.1%) were negative for both H pylori and HAV antibodies (chi(2) = 7.18, OR = 2.8, CI 1.30-5.97). The age adjusted OR for an HAV-infected child being H pylori positive was 2.3 (CI 1.02-5.03). The agreement between H pylori and HAV seropositivity was fair (kappa = 0.24). After controlling for possible confounding, the variables remaining independently associated with seropositivity to H pylori were age, presence of Giardia lamblia in feces (OR = 3.2, 95%CI, 1.1-9.5) and poor garbage disposal quality (OR = 2.4, 95%CI, 1.1-5.1).Our data suggest that H pylori infection is associated with surrogate markers of fecal exposure. Thus, we conclude that the fecal-oral route is relevant in the transmission of HP among children in an urban setting of a developing country. The association observed between G. lamblia and H pylori infection may have several explanations. Further studies to investigate this relationship are warranted.

Pfizer Inc., Brazil Diabetes is a significant public health burden on the basis of its increased incidence, morbidity, and mortality. This study aimed to estimate the prevalence of inadequate glycaemic control and its correlates in a large multicentre survey of Brazilian patients with diabetes. A cross-sectional study was conducted in a consecutive sample of patients aged 18 years or older with either type 1 or type 2 diabetes, attending health centres located in ten large cities in Brazil (response rate = 84%). Information about diabetes, current medications, complications, diet, and satisfaction with treatment were obtained by trained interviewers, using a standardized questionnaire. Glycated haemoglobin (HbA(1c)) was measured by high-performance liquid chromatography in a central laboratory. Patients with HbA(1c) a parts per thousand yen 7 were considered to have inadequate glycaemic control. Overall 6,701 patients were surveyed, 979 (15%) with type 1 and 5,692 (85%) with type 2 diabetes. the prevalence of inadequate glycaemic control was 76%. Poor glycaemic control was more common in patients with type 1 diabetes (90%) than in those with type 2 (73%), P < 0.001. Characteristics significantly associated with improved glycaemic control included: fewer years of diabetes duration, multi professional care, participation in a diabetes health education program, and satisfaction with current diabetes treatment. Despite increased awareness of the benefits of tight glycaemic control, we found that few diabetic patients in Brazil met recommended glycaemic control targets. This may contribute to increased rates of diabetic complications, which may impact health care costs. Our data support the public health message of implementation of early, aggressive management of diabetes. Brazilian Minist Hlth, Oswaldo Cruz Fdn, Goncalo Moniz Res Ctr, BR-40296710 Salvador, BA, Brazil Universidade Federal de São Paulo, BR-04023900 São Paulo, Brazil Pfizer Inc, BR-04717904 São Paulo, Brazil Charitable Works Fdn Sister, Clin Res Ctr, BR-40415006 Salvador, BA, Brazil Universidade Federal de São Paulo, BR-04023900 São Paulo, Brazil Web of Science