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What is this summary about? This is a summary of an article about part of a clinical study for the BNT162b2 COVID-19 vaccine, also called the Pfizer-BioNTech vaccine. The article was published in the New England Journal of Medicine in September 2021. The part of the study described in the article began in July 2020 and is ongoing. This means that the final results may be different from the results included in this summary. What happened in this study? The participants in this study received 2 injections of either the BNT162b2 vaccine or a placebo, 21 days apart. The placebo looked like the BNT162b2 vaccine but had no active vaccine in it. None of the trial participants or study teams knew who received vaccine or placebo. What were the results? Most of the reactions to the injections were mild or moderate and lasted for a short period of time. The most common reactions were pain at the injection site, extreme tiredness (fatigue), and headache. These reactions usually happened in the first 7 days after receiving a vaccine dose. A small number of participants had severe reactions to the vaccine. Compared to participants who received the placebo, participants who received the BNT162b2 vaccine were much less likely to become ill if they were infected with the virus that causes COVID-19. The vaccine also had very good efficacy at preventing severe COVID-19. Participants in South Africa who received the BNT162b2 vaccine were less likely to become ill after infection with the beta variant of the virus compared to participants who received the placebo. The beta variant was very common in South Africa when the study was taking place. Clinical Trial Registration: NCT04368728 ( ClinicalTrials.gov )

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.)

Background Takeda’s dengue vaccine is under evaluation in an ongoing phase 3 efficacy study; we present a 2-year update. Methods Children (20 099, 4–16 years old) were randomized to receive 2 doses of TAK-003 or placebo 3 months apart and are under surveillance to detect dengue by serotype-specific RT-PCR. Results Cumulative efficacy against dengue approximately 27 months since first dose was 72.7% (95% confidence interval [CI], 67.1%–77.3%), including 67.0% (95% CI, 53.6%–76.5%) in dengue-naive and 89.2% (95% CI, 82.4%–93.3%) against hospitalized dengue. In the second year, decline in efficacy was observed (56.2%; 95% CI, 42.3%–66.8%) with the largest decline in 4–5 year olds (24.5%; 95% CI, −34.2% to 57.5%); efficacy was 60.6% (95% CI, 43.8%–72.4%) in 6–11 year and 71.2% (95% CI, 41.0%–85.9%) in 12–16 year age groups. As TAK-003 efficacy varies by serotype, changes in serotype dominance partially contributed to efficacy differences in year-by-year analysis. No related serious adverse events occurred during the second year. Conclusions TAK-003 demonstrated continued benefit independent of baseline serostatus in reducing dengue with some decline in efficacy during the second year. Three-year data will be important to see if efficacy stabilizes or declines further. Clinical Trials Registration. NCT02747927. Takeda’s tetravalent dengue vaccine (TAK-003) continued to demonstrate benefit in reducing dengue independent of baseline serostatus up to 2 years after completing vaccination with some decline in efficacy during the second year in 4–16 year olds in dengue-endemic countries.

Active immunization with the BNT162b2 vaccine (Pfizer-BioNTech) has been a critical mitigation tool against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the coronavirus disease 2019 (Covid-19) pandemic. In light of reports of waning protection occurring 6 months after the primary two-dose vaccine series, data are needed on the safety and efficacy of offering a third (booster) dose in persons 16 years of age or older.In this ongoing, placebo-controlled, randomized, phase 3 trial, we assigned participants who had received two 30-μg doses of the BNT162b2 vaccine at least 6 months earlier to be injected with a third dose of the BNT162b2 vaccine or with placebo. We assessed vaccine safety and efficacy against Covid-19 starting 7 days after the third dose.A total of 5081 participants received a third BNT162b2 dose and 5044 received placebo. The median interval between dose 2 and dose 3 was 10.8 months in the vaccine group and 10.7 months in the placebo group; the median follow-up was 2.5 months. Local and systemic reactogenicity events from the third dose were generally of low grade. No new safety signals were identified, and no cases of myocarditis or pericarditis were reported. Among the participants without evidence of previous SARS-CoV-2 infection who could be evaluated, Covid-19 with onset at least 7 days after dose 3 was observed in 6 participants in the vaccine group and in 123 participants in the placebo group, which corresponded to a relative vaccine efficacy of 95.3% (95% confidence interval, 89.5 to 98.3).A third dose of the BNT162b2 vaccine administered a median of 10.8 months after the second dose provided 95.3% efficacy against Covid-19 as compared with two doses of the BNT162b2 vaccine during a median follow-up of 2.5 months. (Funded by BioNTech and Pfizer; C4591031 ClinicalTrials.gov number, NCT04955626.).

A fully liquid MenACWY-CRM vaccine presentation has been developed, modifying the meningococcal serogroup A (MenA) component from lyophilized to liquid. The safety and immunogenicity of the liquid presentation at the end of the intended shelf-life (aged for 24 or 30 months) were compared to the licensed lyophilized/liquid presentation. This multicenter, randomized (1:1), observer-blind, phase 2b study (NCT03433482) enrolled adolescents and young adults (age 10-40 years). In part 1, 844 participants received one dose of liquid presentation stored for approximately 24 months or licensed presentation. In part 2, 846 participants received one dose of liquid presentation stored for approximately 30 months or licensed presentation. After storage, the MenA free saccharide (FS) level was approximately 25% and O-acetylation was approximately 45%. The primary objective was to demonstrate non-inferiority of the liquid presentation to licensed presentation, as measured by human serum bactericidal assay (hSBA) geometric mean titers (GMTs) against MenA, 1-month post-vaccination. Immune responses against each vaccine serogroup were similar between groups. Between-group ratios of hSBA GMTs for MenA were 1.21 (part 1) and 1.11 (part 2), with two-sided 95% confidence interval lower limits (0.94 and 0.87, respectively) greater than the prespecified non-inferiority margin (0.5), thus meeting the primary study objective. No safety concerns were identified. Despite reduced O-acetylation of MenA and increased FS content, serogroup-specific immune responses induced by the fully liquid presentation were similar to those induced by the licensed MenACWY-CRM vaccine, with non-inferior anti-MenA responses. The safety profiles of the vaccine presentations were similar.

BackgroundBNT162b2 is a lipid nanoparticle-formulated, nucleoside-modified RNA vaccine encoding a prefusion-stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. BNT162b2 is highly efficacious against COVID-19 and is currently authorized for emergency use or conditional approval worldwide. At the time of authorization, data beyond 2 months post-vaccination were unavailable.MethodsIn an ongoing, placebo-controlled, observer-blinded, multinational, pivotal efficacy study, 44,165 ≥16-year-old participants and 2,264 12-15-year-old participants were randomized to receive 2 doses, 21 days apart, of 30 µg BNT162b2 or placebo. Study endpoints reported here are vaccine efficacy (VE) against laboratory-confirmed COVID-19 and safety data, both up to 6 months post-vaccination.ResultsBNT162b2 continued to be safe and well tolerated. Few participants had adverse events leading to study withdrawal. VE against COVID-19 was 91% (95% CI 89.0-93.2) through up to 6 months of follow-up, among evaluable participants and irrespective of previous SARS-CoV-2 infection. VE of 86%-100% was seen across countries and in populations with diverse characteristics of age, sex, race/ethnicity, and COVID-19 risk factors in participants without evidence of previous SARS-CoV-2 infection. VE against severe disease was 97% (95% CI 80.3−99.9). In South Africa, where the SARS-CoV-2 variant of concern, B.1.351 (beta), was predominant, 100% (95% CI 53.5, 100.0) VE was observed.ConclusionWith up to 6 months of follow-up and despite a gradually declining trend in vaccine efficacy, BNT162b2 had a favorable safety profile and was highly efficacious in preventing COVID-19. (ClinicalTrials.govnumber,NCT04368728)

Background Takeda’s live attenuated tetravalent dengue vaccine candidate (TAK-003) is under evaluation in a long-term clinical trial across 8 dengue-endemic countries. Previously, we have reported its efficacy and safety in both seronegative and seropositive participants and that its performance varies by serotype, with some decline in efficacy from first to second year postvaccination. This exploratory analysis provides an update with cumulative and third-year data. Methods Healthy 4–16 year olds (n = 20099) were randomized 2:1 to receive TAK-003 or placebo (0, 3 month schedule). The protocol included baseline serostatus testing of all participants and detection of all symptomatic dengue throughout the trial with a serotype specific reverse transcriptase-polymerase chain reaction. Results Cumulative efficacy after 3 years was 62.0% (95% confidence interval, 56.6–66.7) against virologically confirmed dengue (VCD) and 83.6% (76.8–88.4) against hospitalized VCD. Efficacy was 54.3% (41.9–64.1) against VCD and 77.1% (58.6–87.3) against hospitalized VCD in baseline seronegatives, and 65.0% (58.9–70.1) against VCD and 86.0% (78.4–91.0) against hospitalized VCD in baseline seropositives. Efficacy against VCD during the third year declined to 44.7% (32.5–54.7), whereas efficacy against hospitalized VCD was sustained at 70.8% (49.6–83.0). Rates of serious adverse events were 2.9% in TAK-003 group and 3.5% in placebo group during the ongoing long-term follow-up (ie, second half of the 3 years following vaccination), but none were related. No important safety risks were identified. Conclusions TAK-003 was efficacious against symptomatic dengue over 3 years. Efficacy declined over time but remained robust against hospitalized dengue. A booster dose evaluation is planned.

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.

OBJETIVO: Estimar a incidência de hospitalizações por intoxicação medicamentosa e a mortalidade desses agravos no Brasil, descrevendo as tendências de 2009 a 2018. MÉTODOS: Os dados de internações hospitalares e óbitos originam-se do DATASUS e os dados demográficos, do Instituto Brasileiro de Geografia e Estatística (IBGE). Foram selecionadas as internações hospitalares cuja Autorização para Internação Hospitalar (AIH) indicasse como procedimento “tratamento de intoxicação ou envenenamento por exposição a medicamento e substâncias de uso não medicamentoso”, sendo analisados apenas os casos de hospitalização por intoxicação medicamentosa. A incidência de hospitalização e a mortalidade foram calculadas separadamente para intoxicações causadas por medicamentos com prescrição (MRx) e isentos de prescrição (MIP). As taxas foram ainda estratificadas por sexo, faixa etária e região de residência no Brasil. A análise de tendência foi realizada por regressão linear generalizada pelo método de Prais-Winsten. RESULTADOS: A maioria das internações foi causada por MRx (97%), com mortalidade aproximadamente 50 vezes maior, quando comparada às internações por MIP. A tendência da incidência das internações por MRx foi estacionária, mas a mortalidade aumentou durante o período estudado, enquanto a tendência na mortalidade e na incidência de internações por MIP foi decrescente. CONCLUSÕES: As internações por intoxicação medicamentosa, sobretudo aquelas causadas por MRx, têm grande impacto e importância na saúde pública, especialmente porque esses agravos podem ser prevenidos.

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 After implementation of routine infant MenC vaccination, MenB remains a serious cause of meningococcal disease, yet to be targeted by vaccination programs in several countries. This study (NCT01339923) investigated the immunogenicity and safety of MenC CRM-conjugated vaccine (MenC-CRM) concomitantly administered with MenB vaccine (4CMenB). Methods Infants (N = 251) were randomised 1:1 to receive 4CMenB and MenC-CRM (Group 1) or MenC-CRM alone (Group 2) at 3 and 5 months (M3, M5) and a booster at 12 months of age (M12), and pneumococcal vaccine at M3, M5, M7, M12. Antibody responses to meningococcal vaccines were measured at M3, M6, M12, and M13. Non-inferiority of MenC-CRM response in Group 1 vs Group 2 was demonstrated at M6 and M13, if the lower limit of the 95% confidence interval (LL95%CI) of the difference in percentage of infants with hSBA titres ≥1:8 was >−10%. Sufficiency of MenB response was achieved if LL95%CI of the percentage of infants with hSBA titres ≥1:4 against fHbp, NadA and PorA strains was ≥70% at M6 or ≥75% at M13. Adverse events (AEs) were collected for 7 days post-vaccination, and serious AEs (SAEs) and medically attended AEs throughout the study. Results Non-inferiority of MenC response in Group 1 vs Group 2 (LL95%CI −6.4% [M6]; −5.2% [M13]) and sufficiency of MenB response in Group 1 (LL95%CI 92%, 90%, 89% [M6]; 97%, 92%, 93% [M13] against fHbp, NadA, PorA, respectively) were demonstrated. Higher rates of mild to moderate solicited AEs were reported in Group 1. Unsolicited AEs and SAEs incidences were similar across groups. Conclusions Concomitant administration of MenC-CRM and 4CMenB in infants was immunogenic, resulting in non-inferior responses against MenC compared to MenC-CRM alone and demonstration of sufficient immune response to MenB, after primary and booster vaccination. Reactogenicity was higher for concomitant vaccines administration, but no safety concerns were identified.

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 immunogenicity profile of the 9-valent HPV (9vHPV) vaccine was evaluated across five phase III clinical studies conducted in girls and boys 9â15 years of age and young women 16â26 years of age. The effect of baseline characteristics of subjects on vaccine-induced HPV antibody responses was assessed. Methods: Immunogenicity data from 11,304 subjects who received â¥1 dose of 9vHPV vaccine in five Phase III studies were analyzed. Vaccine was administered as a 3-dose regimen. HPV antibody titers were assessed 1 month after dose 3 using a competitive Luminex immunoassay and summarized as geometric mean titers (GMTs). Covariates examined were age, gender, race, region of residence, and HPV serostatus and PCR status at day 1. Results: GMTs to all 9 vaccine HPV types decreased with age at vaccination initiation, and were otherwise generally similar among the demographic subgroups defined by gender, race and region of residence. For all subgroups defined by race or region of residence, GMTs were higher in girls and boys than in young women. Vaccination of subjects who were seropositive at day 1 to a vaccine HPV type resulted in higher GMTs to that type, compared with those in subjects who were seronegative for that type at day 1. Conclusions: 9vHPV vaccine immunogenicity was robust among subjects with differing baseline characteristics. It was generally comparable across subjects of different races and from different regions. Greater immunogenicity in girls and boys versus young women (the population used to establish 9vHPV vaccine efficacy in clinical studies) indicates that the anti-HPV responses generated by the vaccine in adolescents from all races or regions were sufficient to induce high-level protective efficacy. This immunogenicity profile supports a widespread 9vHPV vaccination program and early vaccination. Studies in the meta-analysis: V503-001, V503-002, V503-005, V503-007, V503-009/GDS01C, Clinical trials.gov identifier: NCT00543543, NCT00943722, NCT00988884, NCT01073293, NCT01304498, Keywords: Human papillomavirus, 9v HPV vaccine, Immunogenicity, Clinical trial

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.

Institute of Biomedical Science. Virology Laboratories. Department of Microbiology. University Hospital. University of São Paulo. Medical School. São Paulo, SP, Brasil University Hospital. University of São Paulo. Medical School. São Paulo, SP, Brasil University Hospital. University of São Paulo. Medical School. São Paulo, SP, Brasil Institute of Tropical Pathology and Public Health. Department of Microbiology, Immunology, Parasitology, and Pathology. Institute of Tropical Pathology and Public Health. Department of Microbiology, Immunology, Parasitology, and Pathology. Federal University of Goias. Department of Pediatrics. Góias, GO, Brasil State Health Secretary. Materno-Infantil Hospital. Goiás, GO, Brasil Federal University of Rio Grande do Sul. Department of Pediatrics. Porto Alegre, RS, Brasil Federal University of Rio Grande do Sul. Department of Pediatrics. Porto Alegre, RS, Brasil Federal University of Rio Grande do Sul. Department of Pediatrics. Porto Alegre, RS, Brasil Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil Irma Dulce Foundation. Salvador, BA, Brasil Global Outcomes Research, Merck. West Point, Pennsylvania Medical Department. MSD Brazil. São Paulo, SP, Brasil Institute of Biomedical Science. Virology Laboratories. Department of Microbiology. BACKGROUND: Rotavirus is a major cause of gastroenteritis in children. Knowledge of rotavirus genotypes is important for vaccination strategies. METHODS: During 2005-2006, rotavirus surveillance studies were conducted in São Paulo, Salvador, Goiânia, and Porto Alegre, Brazil. Stool samples were collected from children

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.

Community-Acquired Pneumonia (CAP) is a major public health problem. In Brazil it has been estimated that 2,000,000 people are affected by CAP every year. Of those, 780,000 are admitted to hospital, and 30,000 have death as the outcome. This is an open-label, non-comparative study with the purpose of evaluating efficacy, safety, and tolerability levels of IV azithromycin (IVA) and IV ceftriaxone (IVC), followed by oral azithromycin (OA) for the treatment of inpatients with mild to severe CAP. Eighty-six patients (mean age 56.6 +/- 19.8) were administered IVA (500 mg/day) and IVC (1g/day) for 2 to 5 days, followed by AO (500 mg/day) to complete a total of 10 days. At the end of treatment (EOT) and after 30 days (End of Study--EOS) the medication was evaluated clinically, microbiologically and for tolerability levels. Out of the total 86-patient population, 62 (72.1%) completed the study. At the end of treatment, 95.2% (CI95: 88.9% - 100%) reported cure or clinical improvement; at the end of the study, that figure was 88.9% (CI95: 74.1% - 91.7%). Out of the 86 patients enrolled in the study, 15 were microbiologically evaluable for bacteriological response. Of those, 6 reported pathogen eradication at the end of therapy (40%), and 8 reported presumed eradication (53.3%). At end of study evaluation, 9 patients showed pathogen eradication (50%), and 7 showed presumed eradication (38.89%). Therefore, negative cultures were obtained from 93.3% of the patients at EOT, and from 88.9% at the end of the study. One patient (6.67% of patient population) reported presumed microbiological resistance. At study end, 2 patients (11.11%) still reported undetermined culture. Uncontrollable vomiting and worsening pneumonia condition were reported by 2.3% of patients. Discussion and Conclusion Treatment based on the administration of IV azithromycin associated to ceftriaxone and followed by oral azithromycin proved to be efficacious and well-tolerated in the treatment of Brazilian inpatients with CAP.

OBJECTIVES 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. SUBJECTS AND METHODS 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. RESULTS 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. CONCLUSION 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.

BACKGROUND: The investigational 9-valent viruslike particle vaccine against human papillomavirus (HPV) includes the HPV types in the quadrivalent HPV (qHPV) vaccine (6, 11, 16, and 18) and five additional oncogenic types (31, 33, 45, 52, and 58). Here we present the results of a study of the efficacy and immunogenicity of the 9vHPV vaccine in women 16 to 26 years of age.METHODS: We performed a randomized, international, double-blind, phase 2b-3 study of the 9vHPV vaccine in 14,215 women. Participants received the 9vHPV vaccine or the qHPV vaccine in a series of three intramuscular injections on day 1 and at months 2 and 6. Serum was collected for analysis of antibody responses. Swabs of labial, vulvar, perineal, perianal, endocervical, and ectocervical tissue were obtained and used for HPV DNA testing, and liquid-based cytologic testing (Papanicolaou testing) was performed regularly. Tissue obtained by means of biopsy or as part of definitive therapy (including a loop electrosurgical excision procedure and conization) was tested for HPV.RESULTS: The rate of high-grade cervical, vulvar, or vaginal disease irrespective of HPV type (i.e., disease caused by HPV types included in the 9vHPV vaccine and those not included) in the modified intention-to-treat population (which included participants with and those without prevalent infection or disease) was 14.0 per 1000 person-years in both vaccine groups. The rate of high-grade cervical, vulvar, or vaginal disease related to HPV-31, 33, 45, 52, and 58 in a prespecified per-protocol efficacy population (susceptible population) was 0.1 per 1000 person-years in the 9vHPV group and 1.6 per 1000 person-years in the qHPV group (efficacy of the 9vHPV vaccine, 96.7%; 95% confidence interval, 80.9 to 99.8). Antibody responses to HPV-6, 11, 16, and 18 were noninferior to those generated by the qHPV vaccine. Adverse events related to injection site were more common in the 9vHPV group than in the qHPV group.CONCLUSIONS: The 9vHPV vaccine prevented infection and disease related to HPV-31, 33, 45, 52, and 58 in a susceptible population and generated an antibody response to HPV-6, 11, 16, and 18 that was noninferior to that generated by the qHPV vaccine. The 9vHPV vaccine did not prevent infection and disease related to HPV types beyond the nine types covered by the vaccine. (Funded by Merck; ClinicalTrials.gov number, NCT00543543).

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.

Introduction 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. Aim 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. Methods 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%). Main Outcome Measures General health, relationships, and sexual behaviors, attitudes, and beliefs. Results 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. Conclusions 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. Moreira ED Jr, Kim S‐C, Glasser D, and Gingell C. Sexual activity, prevalence of sexual problems, and associated help‐seeking patterns in men and women aged 40–80 years in Korea: Data from the Global Study of Sexual Attitudes and Behaviors (GSSAB). J Sex Med 2006;3:201–211.

The Global Study of Sexual Attitudes and Behaviors (GSSAB) investigated various aspects of sex and relationships among 27,500 men and women aged 40-80 years. Here, we report help-seeking behaviours for sexual problems in this population. A questionnaire was administered using the accepted survey method in each country. Although almost half of all sexually active respondents had experienced at least one sexual problem, less than 19% of them (18.0% of men and 18.8% of women) had attempted to seek medical help for their problem(s). The most frequent action taken by men and women was to talk to their partner (39%). Only 9% of men and women had been asked about their sexual health by a doctor in a routine visit during the past 3 years. Although sexual problems are highly prevalent, few men and women seek medical help for these problems. Overall, men and women show similar help-seeking behaviours.

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.

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.

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.

The clinical management of meningitis caused by Escherichia coli is greatly complicated when the organism becomes resistant to broad-spectrum antibiotics. We sought to characterize the antimicrobial susceptibilities, sequence types (ST), and presence of known drug resistance genes of E. coli isolates that caused meningitis between 1996 and 2011 in Salvador, Brazil. We then compared these findings to those for E. coli isolates from community-acquired urinary tract infections (UTI) that occurred during the same time period and in the same city. We found that 19% of E. coli isolates from cases of meningitis and less than 1% of isolates from UTI were resistant to third-generation cephalosporins. The sequence types of E. coli isolates from cases of meningitis included ST131, ST69, ST405, and ST62, which were also found among isolates from UTI. Additionally, among the E. coli isolates that were resistant to third-generation cephalosporins, we found genes that encode the extended-spectrum beta-lactamases CTX-M-2, CTX-M-14, and CTX-M-15. These observations demonstrate that compared to E. coli strains isolated from cases of community-acquired UTI, those isolated from cases of meningitis are more resistant to third-generation cephalosporins, even though the same sequence types are shared between the two forms of extraintestinal infections.

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.

Introduction: Baroreceptors regulate moment-to-moment blood pressure (BP) variations, but their long-term effect on the cardiovascular system and target organ damage remains unclear. Purpose: to investigate the temporal mechanisms enrolled in the relationship between baroreceptor reflex dysfunction and end-organ damage in different pathophysiological conditions as hypertension, heart failure and myocardial infarction. Method: Male Wistar rats were divided into 5 groups: control (n = 9),SAD1(n=8,24h), SAD2(n=8,28 days), SAD3 (n=8, 90 days) and SAD4 (n=7, 6 months). Sinoaortic denervation (SAD) was used as a model of arterial baroreflex deficit. BP, HR were analysed using a data acquisition system (Codas, 2kHz). Cardiac output and tissues blood flow were evaluated using colored microspheres. Result: BP and the HR was incresed in SAD after 24h (C:106 ± 0.6 vs . SAD1: 142 ± 2 mmHg; C: 355 ± 7 vs . SAD1: 453 ± 10 bpm), but it were normalizaed in chronic SAD. Moreover, it was observed a gradual reduction over time in cardiac output (C: 111 ± 7, SAD1:81±5, SAD2:85 ± 6, SAD3:69±5 SAD4:35±2 mL/min) accompanied by an increase in total peripheral resistance (C:0.97±0.07, SAD1:1.74±0.05, SAD2:1.23±0.07, SAD3:1.60±0.09, SAD4:3.00±0.05 mL/min/mmHg) in SAD groups. Those alterations resulted in a decreased renal blood flow (C:3.47±0.21, SAD1:1.37±0.19, SAD2:1.49±0.18, SAD3:1.12±0.13, SAD4:0.42±0.16 mL/min/g) , cardiac blood flow (C:2.91±0.71, SAD1:2.07±0.19, SAD2:1.58±0.28, SAD3:0.92±0.13, SAD4:0.34±0.16 mL/min/g) and muscle blood flow (C:0.24±0.02, SAD1:0.08±0.005, SAD2:0.10±0.02, SAD3:0.05±0.01, SAD4:0.05±0.007 mL/min/g) in SAD groups. Conclusion: The acute total baroreflex dysfuntion incresed BP and HR and reduced blood flow and cardiac output, these changes are associated with the body’s attempt to maintain homeostasis. Howerer, the temporal evaluation showed a progressive reduction in CO and regional blood flow associated with an increase in RPT to maintain blood pressure levels. These adjustements may play an important role in target organ-damage in different pathological conditions, independently of BP levels.

Autonomic and renal dysfunctions are common chronic conditions that frequently coexist in the same individual, and both are associated with significant morbidity and mortality. Aim: To evaluate if total arterial baroreflex abolishment leads to alterations in renal function. Methods: Wistar rats divided into: control (n=9) and SAD (n=9). Sinoaortic denervation (SAD) was performed using the method previously described by Krieger (1964). Metabolic cage was used to evaluate in vivo renal function. BP and HR signals were recorded using a data acquisition system (Codas, 2 kHz). Autonomic function was evaluated by spectral analysis. Colored microspheres (CM) were infused into the left ventricle to determine renal blood flow and resistance changes quantified by spectrophotometry. Ex vivo renal perfusion was used to measure renal function. Results: Neither BP (C: 106 ± 2 vs. SAD: 108 ± 2 mmHg) nor HR (C: 355 ± 7 vs. SAD: 357 ± 15 bpm) were modified by SAD. HRV was decreased in SAD (43 ± 5 vs. C: 103 ± 12 ms2). However, BPV and LF component of BPV, respectly, were increased in SAD (46 ± 10; 6 ± 0.5 mmHg2) compared to C (35 ± 6; 2.6 ± 2 mmHg2). Although BP was similar between groups, it was observed a reduction in cardiac output in denervated animals (85 ± 6 vs. C: 111 ± 7 mL/min, p=0.02) and an increase in total peripheral resistance (1.25 ± 0.03 vs. C: 0.97 ± 0.02 mmHg/mL/min). These alterations resulted in a decreased plasmatic renal flow in SAD group (1.49 ± 0.18 vs. 3.47 ± 0.21 mL/min/g). Water intake and urine volume were higher in SAD (34 ± 1 mL/24h; 26 ± 6 mL) compared to C (25 ± 2 mL/24h; 8 ± 1 mL) and SAD showed proteinuria (0.03 ± 0.01 vs. C: 0.015 ± 0.0005 g/24h). Ex vivo evaluations demonstred a decreased urinary flow (0.07 ± 0.01 vs . C: 0.15 ± 0.01 mL.g-1.min-1) and glomerular filtration rate in SAD group ( 0.5 ± 0.1 vs. C: 0.3 ± 0.01 mL.g-1.min-1). Our data suggest that total baroreflex impairment leads to a renal and peripheral autonomic dysfunction, since SAD induced proteinuria and increased BPV, both markers of functional organ damage. Moreover, even without neurohumoral influence the kidneys from SAD group was not able to work properly. In conclusion, the results obtained in this study provide evidence that the homeostatic role of the baroreflex is essential in the course of changes of renal function.

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.