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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 ≤ 5 lifetime sexual partners. Serum samples were tested for antibodies to HPV6/11/16/18. Swab samples were collected separately from several anogenital areas for detection of HPV6/11/16/18/31/33/35/39/45/51/52/56/58/59 DNA.Results: The prevalence of any tested HPV type was 18.5% at the penis, 17.1% at the scrotum, 33.0% at the perineal/perianal region, 42.4% in the anal canal, and 48.0% at any site. Overall, 415 MSM (69.7%) were negative to HPV 6, 11, 16, and 18 at enrollment by both serology and DNA detection. Men residing in Europe and Latin America had significantly increased risk of HPV infection at external genital sites and the anal canal compared to men from Australia. Tobacco use and greater number of lifetime sexual partners was associated with higher HPV infection prevalence.Conclusions: The prevalence of HPV infection is high among young sexually active MSM, with the anal canal being the most common site of infection. Lifetime number of sexual partners was the most important modifiable risk factor for anogenital HPV infection. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Chikungunya outbreaks have been reported in Brazil since 2014. Adolescents are a sensitive population who would benefit from a prophylactic vaccine. This study assessed the immunogenicity and safety of the vaccine VLA1553 in adolescents in Brazil. With an overall trial duration of 12 months, we now report data on safety and immunogenicity over a period of 28 days after vaccination., Methods: In this double-blind, randomised, placebo-controlled phase 3 trial, adolescents aged 12 to <18 years were recruited. The trial was performed at ten trial sites across Brazil. Eligible participants were generally healthy. The main exclusion criteria comprised immune-mediated or chronic arthritis or arthralgia, a known or suspected defect of the immune system, or any live vaccine received within the 4 weeks before trial vaccination. Randomisation was stratified by baseline serostatus in a 2:1 ratio to receive VLA1553 (at a dose of 1 × 10 4 TCID 50 per 0·5 mL [ie, 50% tissue culture infectious dose]) or placebo. VLA1553 or placebo was administered intramuscularly as a single-dose immunisation on day 1. The primary endpoint was the proportion of baseline seronegative participants with chikungunya virus neutralising antibody levels of 150 or more in μPRNT 50 (a micro plaque reduction neutralisation test), which was considered a surrogate of protection. The safety analysis included all participants receiving a trial vaccination. Immunogenicity analyses were performed in a subset. The trial is registered with ClinicalTrials.gov, NCT04650399., Findings: Between Feb 14, 2022, and March 14, 2023, 754 participants received a trial vaccination (502 received VLA1553 and 252 received placebo) with a per-protocol population of 351 participants for immunogenicity analyses (303 in the VLA1553 group and 48 in the placebo group). In participants who were seronegative at baseline, VLA1553 induced seroprotective chikungunya virus neutralising antibody levels in 247 of 250 (98·8%, 95% CI 96·5-99·8) participants 28 days after vaccination. In seropositive participants, the baseline seroprotection rate of 96·2% increased to 100% after vaccination with VLA1553. Most (365 [93%] of 393) adverse events were of mild or moderate intensity, VLA1553 was generally well tolerated. When compared with placebo, participants exposed to VLA1553 had a significantly higher frequency of related adverse events (351 [69·9%] of 502 vs 121 [48·0%] of 252; p<0·0001), mostly headache, myalgia, fatigue, and fever. Among four reported serious adverse events (three in the VLA1553 group and one in the placebo group), one was classified as possibly related to VLA1553: a high-grade fever. Among 20 adverse events of special interest (ie, symptoms suggesting chikungunya-like disease), 16 were classified as related to trial vaccination (15 in the VLA1553 group and one in the placebo group), with severe symptoms reported in four participants (fever, headache, or arthralgia). 17 adverse events of special interest resolved within 1 week. Among 85 participants with arthralgia (68 in the VLA1553 group and 17 in the placebo group), eight adolescents had short-lived (range 1-5 days), mostly mild recurring episodes (seven in the VLA1553 group and one in the placebo group). The median duration of arthralgia was 1 day (range 1-5 days). The frequency of injection site adverse events for VLA1553 was higher than in the placebo group (161 [32%] vs 62 [25%]), but rarely severe (two [<1%] in the VLA1553 group and one [<1%] in the placebo group). After administration of VLA1553, there was a significantly lower frequency of solicited adverse events in participants who were seropositive at baseline compared with those who were seronegative (53% vs 74%; p<0·0001) including headache, fatigue, fever, and arthralgia., Interpretation: VLA1553 was generally safe and induced seroprotective titres in almost all vaccinated adolescents with favourable safety data in adolescents who were seropositive at baseline. The data support the use of VLA1553 for the prevention of disease caused by the chikungunya virus among adolescents and in endemic areas., Funding: Coalition for Epidemic Preparedness Innovation and EU Horizon 2020., Translation: For the Portuguese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests VB, SH, MaS, MiS, RH, AB, KK, OZ, AP, KD, NW, SE-L, and JCJ are current or former Valneva employees and own stock and/or share options of Valneva. RH, MaS, RM, KD, SE-L, and JCJ are inventors in a patent relevant to the work (patent application number PCT/EP2024/056050 filed at the European Patent Office, The Hague). RM is a consultant of Valneva and received payments. JC declared grants or contracts with Valneva/Butantan, MSD, Sanofi Pasteur, Coalition for Epidemic Preparedness Innovations, Takeda, and National Institutes of Health and honoraria and advisory board participations for Pfizer, Moderna, and Takeda. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: We explored the impact of prior Yellow fever (YF) or Japanese encephalitis (JE) vaccination on the efficacy of Takeda's dengue vaccine candidate, TAK-003 (NCT02747927)., Methods: Children 4-16 years of age were randomized 2:1 to receive TAK-003 or placebo and were under active febrile surveillance. Symptomatic dengue was confirmed by serotype-specific RT-PCR. YF and JE vaccination history was recorded., Results: Of the 20,071 children who received TAK-003 or placebo, 21.1% had a YF and 23.9% had a JE vaccination history at randomization. Fifty-seven months after vaccination, vaccine efficacy was 55.7% (95% CI, 39.7%-67.5%) in those with YF vaccination, 77.8% (70.8%-83.1%) for JE vaccination, and 53.5% (45.4%-60.4%) for no prior YF/JE vaccination. Regional differences in serotype distribution confound these results. The apparent higher vaccine efficacy in the JE vaccination subgroup could be largely explained by serotype-specific efficacy of TAK-003. Within 28 days of any vaccination, the proportions of participants with serious adverse events in the YF/JE prior vaccination population were comparable between the TAK-003 and placebo groups., Conclusions: The available data do not suggest a clinically relevant impact of prior JE or YF vaccination on TAK-003 performance. Overall, TAK-003 was well-tolerated and efficacious in different epidemiological settings., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

The GEMKAP study (2023) unveiled consistent knowledge, attitude, and practice (KAP) levels across Asia-Pacific (APAC) and Latin America (LATAM) countries regarding dengue, with variations in the willingness to vaccinate. Despite an overall KAP parity, the disparities within and between the countries indicated the need for both overarching and tailored strategies. Population-wide gaps in dengue awareness result in suboptimal vaccination priorities and preventive measures. This commentary delves into identifying the drivers and barriers for implementing a multi-pronged dengue prevention and management program, emphasizing the pivotal role of vaccination alongside education and vector control. Drawing on expert interviews in APAC and LATAM, informed by the Consolidated Framework for Implementation Research (CFIR), four key themes emerged: prioritizing and continuously advocating for dengue on national health agendas, fostering stakeholder collaboration, incorporating population perspectives for behavioral change, and designing sustainable dengue prevention and management programs. Successful implementation requires evidence-based decision making and a comprehensive understanding of population dynamics to design adaptive education tailored to diverse population views. This commentary provides actionable strategies for enhancing dengue prevention and management, with a pronounced emphasis on dengue vaccination, advocating for a holistic, population-centric approach for sustained effectiveness.

Background: About half of the world's population lives in dengue-endemic areas. We aimed to evaluate the long-term efficacy and safety of two doses of the tetravalent dengue vaccine TAK-003 in preventing symptomatic dengue disease of any severity and due to any dengue virus (DENV) serotypes in children and adolescents., Methods: In this ongoing double-blind, randomised, placebo-controlled trial, we enrolled healthy participants aged 4-16 years at 26 medical and research centres across eight dengue-endemic countries (Brazil, Colombia, Dominican Republic, Nicaragua, Panama, Philippines, Sri Lanka, and Thailand). The main exclusion criteria were febrile illness (body temperature ≥38°C) at the time of randomisation, hypersensitivity or allergy to any of the vaccine components, pregnancy or breastfeeding, serious chronic or progressive disease, impaired or altered immune function, and previous receipt of a dengue vaccine. Participants were randomly assigned 2:1 (stratified by age and region) using an interactive web response system and dynamic block assignment to receive two subcutaneous doses of TAK-003 or placebo 3 months apart. Investigators, participants, and their parents or legal guardians were blinded to group assignments. Active febrile illness surveillance and RT-PCR testing of febrile illness episodes were performed for identification of virologically confirmed dengue. Efficacy outcomes were assessed in the safety analysis set (all randomly assigned participants who received ≥1 dose) and the per protocol set (all participants who had no major protocol violations), and included cumulative vaccine efficacy from first vaccination to approximately 4·5 years after the second vaccination. Serious adverse events were monitored throughout. This study is registered with ClinicalTrials.gov, NCT02747927., Findings: Between Sept 7, 2016, and March 31, 2017, 20 099 participants were randomly assigned (TAK-003, n=13 401; placebo, n=6698). 20 071 participants (10 142 [50·5%] males; 9929 [49·5%] females; safety set) received TAK-003 or placebo, with 18 257 (91·0%) completing approximately 4·5 years of follow-up after the second vaccination (TAK-003, 12 177/13 380; placebo, 6080/6687). Overall, 1007 (placebo: 560; TAK-003: 447) of 27 684 febrile illnesses reported were virologically confirmed dengue, with 188 cases (placebo: 142; TAK-003: 46) requiring hospitalisation. Cumulative vaccine efficacy was 61·2% (95% CI 56·0-65·8) against virologically confirmed dengue and 84·1% (77·8-88·6) against hospitalised virologically confirmed dengue; corresponding efficacies were 53·5% (41·6-62·9) and 79·3% (63·5-88·2) in baseline seronegative participants (safety set). In an exploratory analysis, vaccine efficacy was shown against all four serotypes in baseline seropositive participants. In baseline seronegative participants, vaccine efficacy was shown against DENV-1 and DENV-2 but was not observed against DENV-3 and low incidence precluded evaluation against DENV-4. During part 3 of the trial (approximately 22-57 months after the first vaccination), serious adverse events were reported for 664 (5·0%) of 13 380 TAK-003 recipients and 396 (5·9%) of 6687 placebo recipients; 17 deaths (6 in the placebo group and 11 in the TAK-003 group) were reported, none were considered study-vaccine related., Interpretation: TAK-003 demonstrated long-term efficacy and safety against all four DENV serotypes in previously exposed individuals and against DENV-1 and DENV-2 in dengue-naive individuals., Funding: Takeda Vaccines., Translations: For the Portuguese, Spanish translations and plain language summary of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests VT, SB, ST, IE, YH, EL, MR, OZ, NF, IL, and DW are, or were, employees of Takeda and hold, or held, stock or stock options in Takeda. PK, CB-T, and XS-L report receiving research grants from Takeda. PK reports receiving research grants from Takeda and funding from Takeda for attending meetings. EDM Jr reports participating in an advisory board for Takeda. DY, HR, CS, PL, LB, MTA, VW, RD, LKF, LR, LMV, VPW, ADF, DG, KL, ALO, and FE declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Immunobridging is an important methodology that can be used to extrapolate vaccine efficacy estimates to populations not evaluated in clinical studies, and that has been successfully used in developing many vaccines. Dengue, caused by a mosquito-transmitted flavivirus endemic to many tropical and subtropical regions, is traditionally thought of as a pediatric disease but is now a global threat to both children and adults. We bridged immunogenicity data from a phase 3 efficacy study of a tetravalent dengue vaccine (TAK-003), performed in children and adolescents living in endemic areas, with an immunogenicity study in adults in non-endemic areas. Neutralizing antibody responses were comparable in both studies following receipt of a two-dose TAK-003 schedule (months 0 and 3). Similar immune responses were observed across exploratory assessments of additional humoral responses. These data support the potential for clinical efficacy of TAK-003 in adults., (© 2023. The Author(s).)

Dengue represents a major public health concern. With effective vaccines in development, it is important to identify motivational factors to maximize dengue vaccine uptake. A cross-sectional, quantitative, electronic survey was administered to a nationally representative adult population ( n = 3800) in Argentina, Brazil, Colombia, Mexico, Indonesia, Malaysia, and Singapore. Willingness to vaccinate against dengue, and Knowledge, Attitudes, and Practices (KAP) toward dengue, vector control, prevention, and vaccination were determined. The Capability, Opportunity, Motivation for Behavior change (COM-B) framework was used to identify factors correlated with dengue vaccine(s) uptake. KAP scores (standardized, 0-100% scale) resulted in a low global score for Knowledge (48%) and Practice (44%), and a moderate score for Attitude (66%); scores were comparable across countries. Of all respondents, 53% had a high willingness (Score: 8-10/10) to vaccinate against dengue, which was higher (59%) in Latin America (Argentina, Brazil, Colombia, Mexico) than in Asia Pacific (40%) (Indonesia, Malaysia, Singapore). Key factors significantly ( p < 0.05) associated with increased willingness to vaccinate included accessibility to the public (subsidies and incentives) and trust in the healthcare system and government. A common approach to dengue prevention across endemic countries--with some country-specific customization, including education, vaccination, and vector control (multi-pronged)--may reduce dengue burden and improve outcomes.

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.

Context: There are few studies of 25-hydroxyvitamin D (25(OH)D) concentrations in healthy adults in Brazil., Objective: This work aimed to estimate the prevalence of vitamin D status and its association with lifestyle, sociodemographic, and anthropometric data in 3 regions of Brazil., Methods: A cross-sectional study was conducted among blood donors of both sexes, living in the cities of Salvador, São Paulo, and Curitiba during summer. Blood samples were collected during the procedure. Serum 25(OH)D and parathyroid hormone (PTH) were measured in the same laboratory using chemiluminescence immunoassays. Lifestyle, sociodemographic, and anthropometric data were gathered by an interview with a standardized questionnaire. Vitamin D deficiency and insufficiency was defined as 25(OH)D levels below 20 ng/mL and below 30 ng/mL, respectively., Results: A total of 1004 healthy adults were evaluated with mean levels of 25(OH)D (28.7 ± 9.27 ng/mL) and PTH (34.4 ± 15.1 pg/mL). The standardized prevalence of vitamin D deficiency and insufficiency was in the study population 15.3% and 50.9%: in Salvador 12.1% and 47.6%, in São Paulo 20.5%, and 52.4% and in Curitiba 12.7% and 52.1%, ( P = .0004). PTH levels were negatively correlated with 25(OH)D levels. Greater body mass index (BMI) and higher latitude were significant predictors of vitamin D deficiency, whereas skin color (White), longer duration of sun exposure, and current use of dietary supplement were protective., Conclusion: This study confirmed the high prevalence of vitamin D deficiency and insufficiency even in the midsummer in a healthy population of Brazil. Vitamin D levels are associated with sun exposure, latitude, BMI, skin color, and use of supplements., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: 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., Methods: 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., Results: 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)., Conclusions: 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.)., (Copyright © 2022 Massachusetts Medical Society.)

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., Competing Interests: Declaration of interests SEG reports speaker honoraria from, and being an investigator for, Merck Sharp & Dohme (MSD) Corp, a subsidiary of Merck & Co (Kenilworth, NJ, USA); being an investigator for Inovio; receiving research support from Medtronic; and being a consultant for THD America. ARG reports receiving grants from MSD paid to her institution and being a member of the scientific advisory board for MSD. JMP reports grants and travel support from MSD during the conduct of the study; grants and personal fees from, and stock options in, Vir Biotechnology; stock options in Virion Therapeutics; and personal fees from Vaccitech, outside the submitted work. MEP reports funding from MSD relating to the conduct of the vaccine trials. EDM has been an investigator for HPV vaccine studies sponsored by MSD and is a member of the scientific advisory board for MSD. EB reports clinical investigator fees for this trial. HJ reports grants and non-financial support from Klinisches Studienzentrum für Infektiologie; personal fees from Hormosan Pharma, GlaxoSmithKline, Ifi-Medizin, and CIP Clinic; grants from Sanofi-Aventis Deutschland, CROMSOURCE, Centre Hospitalier Universitaire de Nantes, and the US Military HIV Research Program (MHRP); grants, personal fees, and non-financial support from, and board membership for, Gilead Sciences; personal fees and non-financial support from, and board membership for, ViiV Healthcare and AbbVie Deutschland; and personal fees and non-financial support from MSD and Janssen-Cilag, all during the conduct of the study. HJ also reports grants, personal fees, and non-financial support from, and board membership for, Gilead Sciences; grants from CROMSOURCE, Centre Hospitalier Universitaire de Nantes, and the US MHRP; personal fees and non-financial support from, and board membership for, ViiV Healthcare and Abbvie Deutschland; and personal fees from GlaxoSmithKline, MSD, Janssen-Cilag, Ifi-Medizin, and CIP Clinic, outside the submitted work. RK reports receiving consultation fees from MSD as a member of the pathology review panel. BMR reports consulting for MSD. MHS reports personal fees from MSD, Roche, Becton Dickinson, and Inovio Pharmaceuticals as a consultant, outside of the submitted work. OB, RD, TG, AL, HJZ, and AS are employees of MSD and might own stock or stock options in Merck. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. Published by Elsevier Ltd.. All rights reserved.)

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.)., (Copyright © 2021 Massachusetts Medical Society.)

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., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

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., (Copyright © 2019. Published by Elsevier Ltd.)

Objective: Examine whether glycaemic control varies according to sex and whether the latter plays a role in modifying factors associated with inadequate glycaemic control in patients with type 2 diabetes (T2D) in Brazil and Venezuela., Design, Setting and Participants: This was a cross-sectional, nationwide survey conducted in Brazil and Venezuela from February 2006 to June 2007 to obtain information about glycaemic control and its determinants in patients with diabetes mellitus attending outpatient clinics., Main Outcome Measures: Haemoglobin A1c (HbA1c) level was measured by liquid chromatography, and patients with HbA1c ≥7.0% (53 mmol/mol) were considered to have inadequate glycaemic control. The association of selected variables with glycaemic control was analysed by multivariate linear regression, using HbA1c as the dependent variable., Results: A total of 9418 patients with T2D were enrolled in Brazil (n=5692) and in Venezuela (n=3726). They included 6214 (66%) women and 3204 (34%) men. On average, HbA1c levels in women were 0.13 (95% CI 0.03 to 0.24; p=0.015) higher than in men, after adjusting for age, marital status, education, race, country, body mass index, duration of disease, complications, type of healthcare, adherence to diet, adherence to treatment and previous measurement of HbA1c. Sex modified the effect of some factors associated with glycaemic control in patients with T2D in our study, but had no noteworthy effect in others., Conclusions: Women with T2D had worse glycaemic control than men. Possible causes for poorer glycaemic control in women compared with men include differences in glucose homeostasis, treatment response and psychological factors. In addition, sex modified factors associated with glycaemic control, suggesting the need to develop specific treatment guidelines for men and women., Competing Interests: Competing interests: EDM reports having received grant support through his institution from Pfizer Inc., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (Copyright © 2018 Merck Sharp & Dohme Corp., and The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Long-term complications of type 1 diabetes mellitus (DM1) can be prevented with adequate glycaemic control. However, high levels of glycated haemoglobin (HbA1c) occur in 60%-90% of the patients with DM1. Thus, we aimed to investigate the role of sociodemographic, behavioural and clinical factors on the HbA1c levels of patients with DM1 in Brazil., Design, Setting and Participants: A cross-sectional study was conducted in ambulatory patients with DM1 aged ≥18 years from 10 Brazilian cities. Sociodemographic, behavioural and clinical data were obtained through interviews., Main Outcome Measures: HbA1c level was measured by liquid chromatography. Hierarchical multiple variable linear regression models were used to identify factors correlated with high levels of HbA1c., Results: Of 979 patients with DM1, 63.8% were women, and the mean age was 40 (SD 14.6) years. The mean HbA1c level was 9.4% (SD 2.2%), and 89.6% of the patients had HbA1c ≥7.0%. Factors independently correlated with increased HbA1c levels included: lower education, non-participation in diabetes classes/lecture during the year before, having a self-perception of poor adherence to diet and insulin, not having private medical care and not measuring the HbA1c levels in the prior year. Of note, poor adherence to diet and insulin were the independent factors most strongly associated with high levels of HbA1c (mean increment in HbA1c levels of 0.88% and 1.25%, respectively)., Conclusion: Poor glycaemic control, which is common among Brazilian patients with DM1, is associated with lower education, self-perception of insufficient adherence to diet and insulin and inadequate monitoring of HbA1c levels. Specific actions, particularly those targeting improving adherence to diet and insulin, may contribute to successful management of patients with DM1., Competing Interests: Competing interests: EDM was a consultant for Pfizer Inc., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

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 5years 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 28days 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 1week and 1month post-dose 4 were 1.25-4.10 and 1.65-4.88-fold higher, respectively, than levels observed 1month following the completion of the three-dose primary series. Seropositivity rates were >99% and 100% at 1week and 1month 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 5years 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., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The immunogenicity profile of the 9-valent HPV (9vHPV) vaccine was evaluated across five phase III clinical studies conducted in girls and boys 9-15 years of age and young women 16-26 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 ≥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., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

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 <0.1%, respectively). Seven deaths were reported; none were considered vaccine related. The proportions of pregnancies with adverse outcome were within ranges reported in the general population., 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., (Copyright © 2016 by the American Academy of Pediatrics.)

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).

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: 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., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

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.

Purpose: To examine the prevalence of lower urinary tract symptoms (LUTS) and the bother they impose in a population-based sample of adults in Brazil., Methods: A cross-sectional population-based survey was conducted between September 2006 and January 2007 in the city of Salvador, Brazil. Cluster samples of representative households were randomly selected for interviews. A structured questionnaire was administered to men and women aged 30 years or older by trained interviewers. Participants were asked about the presence of individual LUTS using current International Continence Society (ICS) definitions and rated their symptom bother. Those with overactive bladder (OAB) also responded the OAB-Validated 8 and the Patient Perception of Bladder Condition questionnaires., Results: Of 3,616 eligible subjects, 3,000 (83%) participated (1,500 men and 1,500 women). OAB was present in 5.1% of men and in 10% of the women, while the prevalence of any LUTS was 81.5 and 84.1%, respectively. The majority of subjects with OAB, 80% of men and 78% of women, reported some bother associated with their urgency symptoms. Overall, storage symptoms were more common than voiding or postmicturition symptoms. Women reported storage symptoms (76.4%) more frequently than men (67.7%), while the opposite was true for voiding (men 39.7%, women 33.7%) and postmicturition (men 30.9%, women 12.8%)., Conclusions: This is the largest population-based survey of LUTS in Brazil, using the 2002 ICS definitions. LUTS prevalence was high and increased with age among both genders in Brazil, whereas the rates of OAB were somewhat lower than previously reported. The high prevalence of urinary symptoms and the bother commonly associated with them highlight their importance to overall well-being.

Background: The importance of tight blood glucose control among outpatients with diabetes mellitus is well established, however, the management of diabetes in the hospital setting is generally considered secondary in importance. This study sought to assess glycemic control and diabetes management in adult patients admitted to hospitals in Brazil., Methods: A cross-sectional and nationwide survey was conducted from July 2010 to January 2012. Eligible cases were 18 years of age or older, had a diagnosis of diabetes and a hospitalization length of stay ≥72 hours. Socio-demographic information, hospitalization details, and data on diabetes diagnosis, management and treatment were collected for all patients by chart review. Information on all blood glucose (BG) readings for a maximum of 20 consecutive days of hospitalization was recorded for each patient., Results: Overall, 2,399 patients were surveyed in 24 hospitals located in 13 cities from all five Brazilian regions. The prevalence of patients presenting hyperglycemic (BG >180 mg/dL) or hypoglycemic (BG <70 mg/dL) events was 89.4% and 30.9% in patients in general wards, and 88.2% and 27.7% in those in Intensive Care Units (ICUs), respectively. In addition, a BG measure >180 mg/dL was recorded in two-thirds of the patient-days. A high proportion of patients were treated with sliding-scale insulin regimen alone in the general wards (52.0%) and in the ICUs (69.2%), and only 35.7% and 3.9% received appropriate insulin therapy in general wards (basal + bolus insulin) and in ICUs (continuous IV insulin), respectively., Conclusions: Inpatient glycemic control and diabetes management needs improvement. Opportunities to improve care in Brazilian hospitals include expanded use of intravenous insulin and subcutaneous basal-bolus insulin protocols, avoiding use of sliding-scale insulin alone, increased frequency of blood glucose monitoring, and institution wide quality improvement efforts targeting both physician and nursing behavior.

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., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

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.

To expand the available panel of recombinant proteins that can be useful for identifying Leishmania-infected dogs and for diagnosing human visceral leishmaniasis (VL), we selected recombinant antigens from L. infantum, cDNA, and genomic libraries by using pools of serum samples from infected dogs and humans. The selected DNA fragments encoded homologs of a cytoplasmic heat-shock protein 70, a kinesin, a polyubiquitin, and two novel hypothetical proteins. Histidine-tagged recombinant proteins were produced after subcloning these DNA fragments and evaluated by using an enzyme-linked immunosorbent assays with panels of canine and human serum samples. The enzyme-linked immunosorbent assays with different recombinant proteins had different sensitivities (67.4-93.0% and 36.4-97.2%) and specificities (76.1-100% and 90.4-97.3%) when tested with serum samples from Leishmania-infected dogs and human patients with VL. Overall, no single recombinant antigen was sufficient to serodiagnosis all canine or human VL cases.

Background: 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<0.001)., Conclusions: Quadrivalent HPV vaccine prevents infection with HPV-6, 11, 16, and 18 and the development of related external genital lesions in males 16 to 26 years of age. (Funded by Merck and others; ClinicalTrials.gov number, NCT00090285.).

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) > or = 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.

Introduction: 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., Aim: 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., Methods: 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., Main Outcome Measures: 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., Results: 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., Conclusions: A review of the currently available evidence from epidemiological studies is provided.

Aims: To determine the prevalence of inadequate glycemic control and its correlates in a large multicenter survey of Venezuelan patients with diabetes., Methods: A cross-sectional study in a sample of adult patients with diabetes, attending health centers in Venezuela. Information about diabetes, current medications, complications, and diet were obtained by trained interviewers, using a standardized questionnaire. HbA(1c) was measured by high-performance liquid chromatography in a central laboratory. Patients with HbA(1c) >or=7% were considered to have inadequate glycemic control., Results: Overall 4075 patients were surveyed, 349(8.6%) with type 1 diabetes (T1D) and 3726(91.4%) with type 2 diabetes(T2D). Subjects' mean age was 58 years, and 65% were female. The prevalence of inadequate glycemic control was 76%. Poor glycemic control was more common in T1D patients (87%) than in those with T2D(75%), p<10(-4). Satisfaction with current diabetes treatment was associated with improved glycemic control among non-insulin-treated patients with T2D, but gender, multi-professional care, and participation in a diabetes education program were not., Conclusions: Despite clinical evidence supporting tight control of diabetes, few diabetic patients in Venezuela met recommended glycemic control targets. This may contribute to increased rates of diabetic complications. Our findings support the public health message of implementation of early, aggressive management of diabetes.

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 <5 years of age who had diarrhea and were screened by the Rotaclone Enzyme Immunoassay for the presence of rotavirus. Confirmed rotavirus-positive samples were characterized for P and G genotypes by reverse-transcriptase polymerase chain reaction., Results: A total of 510 stool samples were collected. Of these, 221 (43.3%) were positive for rotavirus. Overall, G9 was the predominant G type, followed by G2, and G1; P[4] and P[8] were the predominant P types. The most frequent G/P genotype combination detected was G2P[4], followed by G9P[8], G9P[4], and G1P[8]. G2P[4] was the predominant type in Goiânia and Salvador; G9P[8] and G1P[8] were predominant in São Paulo and Porto Alegre, respectively., Conclusions: The prevalence, seasonality, and genotype distribution of rotavirus infection varied in different regions in Brazil. With immunization programs, continuous monitoring of rotavirus types is important to detect novel and emerging strains.

Objectives: To report the sexual activity, the prevalence of sexual problems and related help-seeking behavior among adults in France., Methods: A telephone survey was conducted in 2001 and 2002. Interviews were based on a standardized questionnaire including demographic details, overall health, relationships, and sexual behaviors, attitudes and beliefs., Results: A total of 1500 individuals (750 men, 750 women) aged 40 to 80 years completed the survey. Eighty-one percent of men and 65% of women had engaged in sexual intercourse during the 12 months preceding the interview. Premature ejaculation (16%) and erectile dysfunction (15%) were the most frequently reported sexual problems among men. Lack of sexual interest (21%) and a lack of sexual pleasure (18%) were the most frequently reported ones among women. Only 10% of men and 8% of women had been asked by a doctor about possible sexual problems during a routine visit in the last 3 years., Conclusions: Many middle aged and older men and women in France report continued sexual interest and activity. Although a number of sexual problems are seen in this population, only a minority of 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, and/or a lack of awareness of available treatments.

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.

We assessed the susceptibility of Escherichia coli strains causing communityacquired urinary tract infection (UTI) in a large urban center in Brazil, comparing two different populations (patients with health insurance vs. uninsured). 581 nonduplicate strains of E. coli were isolated. The prevalence of antimicrobial resistance was greater than 20% for ampicillin (51%), trimethoprim-sulfamethoxazole (43%), tetracycline (41%) and chloramphenicol (22%). Overall, 12% of the E. coli isolates were resistant to ciprofloxacin. Resistance prevalences to most antimicrobials were similar in the two study populations. Our data provide much needed information on the prevalence of antimicrobial resistance among E. coli causing communityacquired UTI in Brazil. Antimicrobial resistance among strains of E. coli causing community-acquired UTIs was relatively high, particularly resistance to ciprofloxacin.

Objective: To evaluate a possible correlation between the International Prostate Symptom Score (IPSS) and the Sexual Health Inventory for Men (SHIM) in an unselected population of men presenting to a clinic, as lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) are highly prevalent in ageing men, and recent largely community-based epidemiological studies reported a close association between ED and LUTS., Patients and Methods: This was a cross-sectional study in an unselected consecutive sample of 118 men aged >40 years attending a urology clinic; the reason for consulting was not ascertained. While in the waiting room the men were asked to participate in the study and on agreement were given the IPSS and the SHIM to complete., Results: The mean (range) age of the participants was 61.7 (45-82) years. Overall, 19 (16%) and 47 (40%) of the men reported having moderate or severe LUTS, respectively. Erectile problems were also common, the prevalence of moderate ED was 11% and complete ED 29%. The Pearson correlation coefficient between the IPSS and the SHIM was - 0.32 (P < 0.001)., Conclusion: There was a close correlation between the IPSS and SHIM in this unselected population of men, adding evidence favouring a close association between LUTS and ED.

Objectives: To evaluate the level of symptoms of lower urinary tract dysfunction (LUTD) in orphans in institutions, and compare these data with schoolchildren of the same age group who were not institutionalised, as LUTD in children is related to factors such as social isolation and low self-esteem, with other psychological changes also being cited, although it is unknown whether these problems are primary or secondary to the symptoms of LUTD., Patients and Methods: Children institutionalised in orphanages with no parental presence and who are isolated from a family environment are probably more sensitive to psychological disturbances. Psychological changes have been associated with symptoms of urgency and urinary incontinence. Thus 89 orphans were compared with 143 schoolchildren not in institutions. A questionnaire was devised and completed by the care-taking staff in the orphanage, while for the schoolchildren the parents completed the questionnaire. The mean age in the institutionalised children was 7.9 years and that of the control group 7.8 years (P = 0.32). Thirty-nine (44%) of the orphans were boys, vs 74 (54%) of the control group (P = 0.17)., Results: The incidence of urgency, diurnal urinary incontinence, nocturnal enuresis and constipation in the orphans and in the control group were: 45 (51%) and 57 (40) (P = 0.17), 36 (40%) and 19 (13%) (P < 0.001), 39 (47%) and 38 (27%) (P = 0.002), and 27 (30%) and 43 (30%) (P = 0.76), respectively., Conclusion: Children living in orphanages have a significantly higher level of diurnal urinary incontinence and nocturnal enuresis than those not in an institution.

Study Objective: To assess knowledge and attitudes of young uninsured women toward human papillomavirus (HPV) vaccination and clinical trials., Design: Cross-sectional study., Setting: Clinic-based sample in Brazil., Participants: A consecutive sample of 204 women aged 16 to 23 years, attending a public outpatient gynecological clinic., Interventions: A questionnaire administered by in-person interview., Main Outcome Measures: Data on knowledge and attitudes towards HPV vaccination., Results: Overall, 72% of the respondents would enroll in a HPV vaccine trial, despite the fact that 69% of women were ignorant of what HPV may cause, and only 10% acknowledged that HPV might lead to cervical cancer. The need of a placebo arm (31%) and three vaccinations injections (26%) were the trial design characteristics most cited for deterring participation. Factors promoting participation were "careful/detailed consultations by the same physician" (92%), "access to more information on women's health" (84%), and "office visits on time" (79%); whereas "clinic too far from home" (36%), "fear of adverse events" (29%), and "gynecologic examination discomfort" (25%) were the most commonly reported reasons for not enrolling in a trial. Being sexually active, more than three lifetime sexual partners and perception of high risk for cervical cancer were predictors of participation in a HPV vaccine trial., Conclusions: Knowledge of HPV infection and cervical cancer is low in this urban, young population. Thus, when planning HPV vaccine trials, it is important to consider implementing educational programs to provide knowledge of the benefits of a preventive vaccine and information on the etiology of and risk factors for cervical cancer.

The objective of the study was to assess knowledge and attitudes about human papillomavirus (HPV), cervical cancer, and Papanicolaou (Pap) smears among young women. A questionnaire was administered to 204 women aged 16-23 years, attending a public clinic. Data were gathered on sociodemographic characteristics, knowledge, and attitudes related to HPV. Overall, 92% of women reported current/previous sexual activity, 42% perceived themselves at high risk of acquiring a sexually transmitted disease, 67% did not know that HPV can cause cervical cancer/warts, and only 10% acknowledged that HPV might lead to cervical cancer. In general, women had a poor knowledge on HPV diagnosis/treatment, condyloma signs, and Pap smear test. The main reasons for not having a Pap smear test done before were embarrassment (63%) and fear of pain (61%). Knowledge of HPV infection and cervical cancer was low in this urban young population. Our findings recommend for greater HPV education of the public and health care practitioners.