Efficacy, immunogenicity, and safety of a quadrivalent HPV vaccine in men: results of an open-label, long-term extension of a randomised, placebo-controlled, phase 3 trial.

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.

Adiposity and pathogen exposure: An investigation of response to iron supplementation and hypothesized predictors in anemic pre-school-aged children living in a dual burden environment.

OBJECTIVES: Peruvians are experiencing rapid dietary and lifestyle changes, resulting in a phenomenon known as the "dual burden of disease." A common manifestation of the dual burden in individuals is the co-occurrence of overweight and anemia. Despite recent initiatives introduced to address these concerns, rates continue to be public health concerns. This study investigates the relationship between immune activation and lack of response to iron supplementation after 1 month of treatment and explores variation in body fat stores as a potential moderator between immune function and response to treatment. METHODS: Data come from children, aged 2-5 years (n = 50) from a peri-urban community in Lima, Peru. Multivariate logistic regression models were used to explore the associations between response to treatment (Hb > =11.0 g/dl) after 1 month of treatment), markers of immune activation (C-reactive protein [CRP] and reported morbidity symptoms), and measures of body fat (waist-to-height ratio, triceps skinfold thickness, and body mass index [BMI]). RESULTS: We found that high CRP is associated with a lack of response to iron supplementation after 1 month of treatment and that BMI z-score may moderate this association. Generally, larger body size is associated with response to iron supplementation whether or not the children in this sample have high immune activation. However, the probability of anemic children responding to iron supplementation treatment differed across adiposity measures. CONCLUSIONS: Our finding suggesting that adiposity and CRP influence response to iron supplementation, furthers our understanding of the relationship between inflammation and anemia treatment in children and has both theoretical and public health implications.

Iron and infection: An investigation of the optimal iron hypothesis in Lima, Peru.

OBJECTIVES: This article explores the optimal iron hypothesis through secondary data analysis of the association between hemoglobin levels and morbidity among children living in Canto Grande, a peri-urban community located on the outskirts of Lima, Peru. METHODS: Risk ratios were used to test whether lower iron status, assessed using the HemoCue B-Hemoglobin System, was associated with an increased relative risk of morbidity symptoms compared to iron replete status, controlling for infant age, sex, weight for height z-score, maternal education, and repeated measures in 515 infants aged 6-12 months. RESULTS: Infants with fewer current respiratory and diarrheal morbidity symptoms had a lower risk of low iron deficiency compared to participants who were iron replete (P < .10). Infants with fewer current respiratory infection symptoms had a statistically significant (P < .05) reduction in risk of moderate iron deficiency compared to infants who were iron replete. CONCLUSION: In this study, morbidity status was not predictive of iron deficient status over a six-month interval period, but nonreplete iron status was shown to be associated with current morbidity symptoms. These results support investigating iron status as an allostatic system that responds to infection adaptively, rather than expecting an optimal preinfection value.

Strengthening health services to deliver nutrition education to promote complementary feeding and healthy growth of infants and young children: formative research for a successful intervention in peri-urban Trujillo, Peru.

Formative research is critical for developing effective nutrition-specific interventions to improve infant and young child (IYC) feeding practices and promote healthy growth. Health workers interact with caregivers during health facility visits, yet there is limited research about how to optimize delivery of such interventions during these visits. The extensive reach of IYC health services globally calls for research to address this gap. In Trujillo, Peru, formative research was conducted to explore complementary feeding practices with caregivers as well as health worker routines and interactions with caregivers related to feeding and healthy growth; results informed the development and delivery of an educational intervention. Multiple qualitative methods were used to collect data on a purposive sample of health workers and caregivers from three health facilities and communities: household trials followed. Complementary feeding messages with doable behaviours were developed, and three were selected as key to promote based on their nutritional impact and cultural acceptability. In the health facilities, medical consultation, well-child visits and nutrition consultation all dealt with aspects of IYC nutrition/growth during their interactions with caregivers but were independent and inconsistent in approach. A nutrition education strategy was developed based on consistency, quality and coverage in the IYC health services. We conclude that formative research undertaken in the community and IYC health services was critical to developing a successful and culturally relevant intervention to promote optimal complementary feeding practices and healthy growth during interactions between health workers and caregivers at routine health facility visits. © 2016 John Wiley & Sons Ltd.

Prevalence of childhood overweight and obesity and associated factors in Peru / Prevalencia de sobrepeso y obesidad infantiles y de sus factores asociados en el Perú

OBJECTIVE:To determine the prevalence of and factors associated with childhood overweight and obesity among a cohort of children 7-8 years of age in Peru. METHODS: This was a cross-sectional secondary analysis of data from the Young Lives longitudinal study of childhood poverty. The sample was a cohort of 1 737 children 7-8 years of age in 2009. Prevalence of overweight and obesity was assessed using body mass index-forage Z-scores. Logistic regression was used to determine associations with a number of individual, household, and community factors. RESULTS: Prevalences of overweight and obesity were 19.2% and 8.6%, respectively. A prevalence of 32.0% and 23.5% overweight and obesity was found among males and females, respectively. High socioeconomic status, living in Lima, having a mother who was overweight or obese, being male, and being an only child or having only one sibling were associated with being overweight and obese at this age. CONCLUSIONS: This study shows a high prevalence of childhood and maternal overweight and obesity in Peru. In contrast to findings in many high-income countries, the findings in Peru indicate that children from wealthier households were more likely to be overweight or obese than those from poorer households. In addition, there is something particularly obesogenic about the Lima environment that merits further investigation, and several key issues to consider when targeting future interventions and research.

OBJETIVO:Determinar la prevalencia de sobrepeso y obesidad infantiles y de sus factores asociados en una cohorte de niños de 7 y 8 años de edad en el Perú. MÉTODOS: El presente estudio es un análisis secundario, de tipo transversal, de los datos generados por el ensayo longitudinal sobre la pobreza en la niñez conocido por Vidas jóvenes. La muestra se compuso de una cohorte de 1 737 niños que tenían 7 y 8 años de edad en 2009. La prevalencia de sobrepeso y obesidad se evaluó mediante el uso de la puntuación z del índice de masa corporal para la edad. Se llevó a cabo una regresión logística con objeto de detectar posibles asociaciones con diversos factores individuales, domésticos y comunitarios. RESULTADOS: El sobrepeso y la obesidad mostraron prevalencias de 19,2% y 8,6%, respectivamente. Se halló una prevalencia de sobrepeso y obesidad de 32,0% y 23,5% en niños y niñas, respectivamente. Varios factores mostraron una asociación con el sobrepeso y la obesidad a esta edad: pertenecer a un estrato socioeconómico alto; vivir en Lima; tener una madre con sobrepeso u obesidad; ser de sexo masculino; y ser hijo único o tener un solo hermano o hermana. CONCLUSIONES: El presente estudio pone de manifiesto la alta prevalencia de obesidad materna e infantil en el Perú. Los resultados observados en este país, que contrastan con los provenientes de muchos países de ingresos altos, apuntan a una mayor propensión al exceso de peso o a la obesidad entre los niños de hogares más ricos que entre los de hogares más pobres. Además, existe algún factor especialmente obesógeno en el ambiente de Lima que debe investigarse más a fondo, así como varios factores esenciales que deberán tenerse en cuenta a la hora de determinar cómo enfocar las intervenciones e investigaciones en un futuro.

Phase II studies to select the formulation of a multivalent HPV L1 virus-like particle (VLP) vaccine.

Our objective was to develop a multivalent prophylactic HPV vaccine that protects against infection and disease caused by HPV16/18 (oncogenic types in existing prophylactic vaccines) plus additional oncogenic types by conducting 3 Phase II studies comparing the immunogenicity (i.e., anti-HPV6/11/16/18 geometric mean titers [GMT]) and safety of 7 vaccine candidates with the licensed quadrivalent HPV6/11/16/18 vaccine (qHPV vaccine) in young women ages 16-26. In the first study (Study 1), subjects received one of 3 dose formulations of an 8-valent HPV6/11/16/18/31/45/52/58 vaccine or qHPV vaccine (control). In Study 2, subjects received one of 3 dose formulations (termed low-, mid-, and high-dose formulations, respectively) of a 9-valent HPV6/11/16/18/31/33/45/52/58 vaccine (9vHPV vaccine) or qHPV vaccine (control). In Study 3, subjects concomitantly received qHPV vaccine plus 5-valent HPV31/33/45/52/58 or qHPV vaccine plus placebo (control). All vaccines were administered at day 1/month 2/month 6. In studies 1 and 3, anti-HPV6/11/16/18 GMTs at month 7 were non-inferior in the experimental arms compared with the control arm; however, there was a trend for lower antibody responses for all 4 HPV types. In Study 2, this immune interference was overcome with the mid- and high-dose formulations of the 9vHPV vaccine by increasing antigen and adjuvant doses. In all 3 studies, all vaccine candidates were strongly immunogenic with respect to HPV31/33/45/52/58 and were well tolerated. Based on the totality of the results, the middle dose formulation of the 9vHPV vaccine was selected for Phase III evaluation. Each 0.5mL dose contains 30µg/40µg/60µg/40µg/20µg/20µg/20µg/20µg/20µg of HPV6/11/16/18/31/33/45/52/58 virus-like particles, and 500µg of amorphous aluminum hydroxyphosphate sulfate adjuvant.ClinicalTrials.gov numbers NCT00260039, NCT00543543, and NCT00551187.

Screen-and-treat approach to cervical cancer prevention using visual inspection with acetic acid and cryotherapy: experiences, perceptions, and beliefs from demonstration projects in Peru, Uganda, and Vietnam.

Cervical cancer is preventable but continues to cause the deaths of more than 270,000 women worldwide each year, most of them in developing countries where programs to detect and treat precancerous lesions are not affordable or available. Studies have demonstrated that screening by visual inspection of the cervix using acetic acid (VIA) is a simple, affordable, and sensitive test that can identify precancerous changes of the cervix so that treatment such as cryotherapy can be provided. Government partners implemented screening and treatment using VIA and cryotherapy at demonstration sites in Peru, Uganda, and Vietnam. Evaluations were conducted in the three countries to explore the barriers and facilitating factors for the use of services and for incorporation of screen-and-treat programs using VIA and cryotherapy into routine services. Results showed that use of VIA and cryotherapy in these settings is a feasible approach to providing cervical cancer prevention services. Activities that can help ensure successful programs include mobilizing and educating communities, organizing services to meet women's schedules and needs, and strengthening systems to track clients for follow-up. Sustainability also depends on having an adequate number of trained providers and reducing staff turnover. Although some challenges were found across all sites, others varied from country to country, suggesting that careful assessments before beginning new secondary prevention programs will optimize the probability of success.

Screen-and-treat approach to cervical cancer prevention using visual inspection with acetic acid and cryotherapy: experiences, perceptions, and beliefs from demonstration projects in Peru, Uganda, and Vietnam.

Cervical cancer is preventable but continues to cause the deaths of more than 270,000 women worldwide each year, most of them in developing countries where programs to detect and treat precancerous lesions are not affordable or available. Studies have demonstrated that screening by visual inspection of the cervix using acetic acid (VIA) is a simple, affordable, and sensitive test that can identify precancerous changes of the cervix so that treatment such as cryotherapy can be provided. Government partners implemented screening and treatment using VIA and cryotherapy at demonstration sites in Peru, Uganda, and Vietnam. Evaluations were conducted in the three countries to explore the barriers and facilitating factors for the use of services and for incorporation of screen-and-treat programs using VIA and cryotherapy into routine services. Results showed that use of VIA and cryotherapy in these settings is a feasible approach to providing cervical cancer prevention services. Activities that can help ensure successful programs include mobilizing and educating communities, organizing services to meet women's schedules and needs, and strengthening systems to track clients for follow-up. Sustainability also depends on having an adequate number of trained providers and reducing staff turnover. Although some challenges were found across all sites, others varied from country to country, suggesting that careful assessments before beginning new secondary prevention programs will optimize the probability of success.

Parental acceptance of HPV vaccine in Peru: a decision framework.

OBJECTIVE AND METHOD: Cervical cancer is the third most common cancer affecting women worldwide and it is an important cause of death, especially in developing countries. Cervical cancer is caused by human papillomavirus (HPV) and can be prevented by HPV vaccine. The challenge is to expand vaccine availability to countries where it is most needed. In 2008 Peru's Ministry of Health implemented a demonstration project involving 5(th) grade girls in primary schools in the Piura region. We designed and conducted a qualitative study of the decision-making process among parents of girls, and developed a conceptual model describing the process of HPV vaccine acceptance. RESULTS: We found a nonlinear HPV decision-making process that evolved over time. Initially, the vaccine's newness, the requirement of written consent, and provision of information were important. If information was sufficient and provided by credible sources, many parents accepted the vaccine. Later, after obtaining additional information from teachers, health personnel, and other trusted sources, more parents accepted vaccination. An understanding of the issues surrounding the vaccine developed, parents overcome fears and rumors, and engaged in family negotiations-including hearing the girl's voice in the decision-making process. The concept of prevention (cancer as danger, future health, and trust in vaccines) combined with pragmatic factors (no cost, available at school) and the credibility of the offer (information in the media, recommendation of respected authority figure) were central to motivations that led parents to decide to vaccinate their daughters. A lack of confidence in the health system was the primary inhibitor of vaccine acceptance. CONCLUSIONS: Health personnel and teachers are credible sources of information and can provide important support to HPV vaccination campaigns.

Human papillomavirus vaccine delivery strategies that achieved high coverage in low- and middle-income countries.

OBJECTIVE: To assess human papillomavirus (HPV) vaccination coverage after demonstration projects conducted in India, Peru, Uganda and Viet Nam by PATH and national governments and to explore the reasons for vaccine acceptance or refusal. METHODS: Vaccines were delivered through schools or health centres or in combination with other health interventions, and either monthly or through campaigns at fixed time points. Using a two-stage cluster sample design, the authors selected households in demonstration project areas and interviewed over 7000 parents or guardians of adolescent girls to assess coverage and acceptability. They defined full vaccination as the receipt of all three vaccine doses and used an open-ended question to explore acceptability. FINDINGS: Vaccination coverage in school-based programmes was 82.6% (95% confidence interval, CI: 79.3-85.6) in Peru, 88.9% (95% CI: 84.7-92.4) in 2009 in Uganda and 96.1% (95% CI: 93.0-97.8) in 2009 in Viet Nam. In India, a campaign approach achieved 77.2% (95% CI: 72.4-81.6) to 87.8% (95% CI: 84.3-91.3) coverage, whereas monthly delivery achieved 68.4% (95% CI: 63.4-73.4) to 83.3% (95% CI: 79.3-87.3) coverage. More than two thirds of respondents gave as reasons for accepting the HPV vaccine that: (i) it protects against cervical cancer; (ii) it prevents disease, or (iii) vaccines are good. Refusal was more often driven by programmatic considerations (e.g. school absenteeism) than by opposition to the vaccine. CONCLUSION: High coverage with HPV vaccine among young adolescent girls was achieved through various delivery strategies in the developing countries studied. Reinforcing positive motivators for vaccine acceptance is likely to facilitate uptake.

Effect of a two-component intervention to change hospital practice from early to delayed umbilical cord clamping in the Peruvian Amazon / Efecto de una intervención de dos componentes para modificar la práctica hospitalaria de pinzamiento del cordón umbilical de precoz a tardío en la Amazonia peruana

OBJECTIVE: To investigate the effect of a two-component intervention to change hospital practice with regard to the timing of umbilical cord clamping. METHODS: A pre-/post-study design was used to measure the effect of a two-component intervention on mean time to clamp the umbilical cord. The study took place at Hospital Iquitos "César Garayar García" in Iquitos, Peru. A total of 224 women were recruited from the hospital labor room: 112 pre-intervention, from 18 May-3 June 2009, and 112 post-intervention, from 6-20 July 2009. The intervention consisted of 1) a "best practice" three-day training workshop on birthing, and 2) a hospital directive. All deliveries were observed and the time between delivery of the first shoulder and clamping of the umbilical cord was measured with a digital stopwatch. RESULTS: The mean time between delivery and cord clamping before the intervention was 56.8 seconds (95 percent confidence interval [CI]: 51.0, 62.7). This increased to 169.8 seconds (95 percent CI: 153.8, 185.8) following the intervention. The difference in mean time to clamp remained significant in multivariate analyses (βadjusted = 113.2 seconds, 95 percent CI: 96.6, 129.9). CONCLUSIONS: Hospital policy and practice can be successfully changed from early to delayed umbilical cord clamping using a simple, two-component intervention.

OBJETIVO: Investigar el efecto de una intervención de dos componentes para modificar la práctica hospitalaria respecto del momento en que se practica el pinzamiento del cordón umbilical. MÉTODOS: Se empleó un estudio con diseño antes-después para medir el efecto de una intervención de dos componentes sobre el tiempo medio de pinzamiento del cordón umbilical. El estudio se llevó a cabo en el Hospital Iquitos "César Garayar Gar-cía" en Iquitos (Perú). Se incluyeron en total 224 mujeres atendidas en la sala de trabajo de parto del hospital: 112 antes de la intervención, entre el 18 de mayo y el 3 de junio del 2009, y 112 después de la intervención, entre el 6 y el 20 de julio del 2009. La intervención consistió en: 1) un taller de capacitación sobre las "mejores prácticas" en la atención del parto, de 3 días de duración y 2) una directiva del hospital. Se observaron todos los partos y se midió el tiempo entre la salida del hombro anterior y el pinzamiento del cordón umbilical con un cronómetro digital. RESULTADOS: El tiempo medio entre el parto y el pinzamiento del cordón antes de la intervención fue de 56,8 segundos (intervalo de confianza [IC] de 95 por cento: 51,0-62,7), y aumentó a 169,8 segundos (IC 95 por cento: 153,8-185,8) después de la intervención. La diferencia en el tiempo medio hasta el pinzamiento siguió siendo significativa en los análisis multivariados (βajustado = 113,2 segundos, IC 95 por cento: 96,6-129,9). CONCLUSIONES: Es posible cambiar las normas y las prácticas hospitalarias de pinzamiento del cordón umbilical de precoz a tardío mediante una intervención sencilla de dos componentes.

Efficacy of quadrivalent HPV vaccine against HPV Infection and disease in males.

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.).

External genital human papillomavirus prevalence and associated factors among heterosexual men on 5 continents.

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.

Formative research to shape HPV vaccine introduction strategies in Peru / Investigación formativa relacionada con el diseño de estrategias para introducir la vacuna contra el VPH en Perú

OBJECTIVE: To understand the sociocultural environment, health systems' capacities, and policy processes related to cervical cancer and HPV vaccines in order to inform HPV vaccine introduction. MATERIAL AND METHODS: Mixed-method formative research using qualitative and quantitative data collection techniques. Participants included girls, parents, community leaders, health and education officials, and policymakers. RESULTS: Respondents, including policymakers, generally supported HPV vaccine introduction, due partly to appreciation for the benefits of vaccination and the desire to prevent cancer. Community-level concerns regarding safety and quality of services will need to be addressed. The immunization system in Peru is strong and has capacity for including the HPV vaccine. CONCLUSION: Formative research provides key insights to help shape an effective program for HPV vaccine introduction.

OBJETIVO: Comprender el contexto sociocultural, las capacidades del sistema de salud y las condiciones políticas vinculadas al cáncer cervical y a la vacuna contra el VPH para diseñar una estrategia apropiada de introducción de la vacuna contra el VPH. MATERIAL Y MÉTODOS: Investigación formativa usando técnicas cualitativas y cuantitativas. Los participantes incluyeron niños, padres, líderes, funcionarios del sector salud y educación, y diseñadores de políticas. RESULTADOS: Generalmente se apoya la introducción de la vacuna contra el VPH, dado que se aprecian los beneficios de la vacunación y se desea prevenir el cáncer. En la comunidad se encontraron preocupaciones sobre seguridad, confianza y calidad de atención. El sistema de inmunizaciones en el Perú es eficiente y tiene la capacidad para incluir la vacuna contra el VPH. CONCLUSIONES: La investigación formativa permite comprender elementos clave que ayudan a diseñar un programa efectivo para la introducción de la vacuna contra el VPH.

Formative research to shape HPV vaccine introduction strategies in Peru.

OBJECTIVE: To understand the sociocultural environment, health systems' capacities, and policy processes related to cervical cancer and HPV vaccines in order to inform HPV vaccine introduction. MATERIAL AND METHODS: Mixed-method formative research using qualitative and quantitative data collection techniques. Participants included girls, parents, community leaders, health and education officials, and policymakers. RESULTS: Respondents, including policymakers, generally supported HPV vaccine introduction, due partly to appreciation for the benefits of vaccination and the desire to prevent cancer. Community-level concerns regarding safety and quality of services will need to be addressed. The immunization system in Peru is strong and has capacity for including the HPV vaccine. CONCLUSION: Formative research provides key insights to help shape an effective program for HPV vaccine introduction.

Can coca leaves contribute to improving the nutritional status of the Andean population?

BACKGROUND: Coca leaves (Erythroxylum coca) have been promoted as a food that could address the dietary deficiencies of the Andean population, but this is based on nutrient analyses of a small sample of leaves. OBJECTIVE: We assessed the nutritional potential of eight samples of coca leaves grown in different regions of Peru. METHODS: We used AOAC techniques to measure nutrients, nutrient inhibitors (phytate, polyphenols, oxalic acid, and fiber), and alkaloid concentrations, all expressed per 100 g dry weight (DW) of the ground leaves. Minerals were measured by inductively coupled lasma- mass spectrometry in n twondependent laboratories. RESULTS: The leaves contained protein, , 20.28 g/1 0DW with lysine as the limiting amino acid; n-cbetarotene, 3.51 mg/100gDW ; vitamin E, 16.72 mg/100gDW ; trace amounts of vitamin D; calcium, 990.18 and 1033.17 mg/100 gDW at two different laboratories; iron, 29.16 and 29.16 mg/100 gDW; zinc, 2.71 and 2.63 mg/100 gDW; and magnesium, 225.19 and 196.69 mg/l001gDW Cocaine was the principal alkaloid, with a concentration of 0.56 g/100 gDW; other alkaloids were also identified. The results were compared with those for other edible leaves. The nutrient contributions of coca powder (5 g) and bread made with coca were compared with those of normal portions of alternative foods. CONCLUSIONS: Two spoonfuls of coca leaf flour would satisfy less than 10% of dietary intakes for schoolchildren and adults for critical commonly deficient nutrients in the diet. Coca leaves do not provide nutritional benefits when eaten in the recommended quantities, and the presence of absorbable cocaine and other alkaloids may be potentially harmful; hence coca leaves cannot be recommended as a food.

Determinants of human papillomavirus vaccine acceptability in Latin America and the Caribbean.

Prophylactic human papillomavirus (HPV) vaccines provide promise as a key component of future cervical cancer prevention programs in the Latin America and the Caribbean region. The successful introduction and acceptance of these vaccines will depend on a range of factors including awareness of cervical cancer as a problem, affordability of the vaccine, political will, competition with other vaccines, feasibility of vaccine delivery and acceptability of the vaccine among the range of groups who will influence uptake. While existing data about acceptability from Latin America and the Caribbean is scarce, it is clear that health policymakers, providers and the general public lack knowledge about HPV and cervical cancer. Furthermore, they would value more local epidemiologic data related to cervical cancer. Price is currently a major barrier to vaccine acceptability and a priority for advocacy. More research is required in Latin America and the Caribbean to determine what messages and strategies will work in these communities.

Implementation examined in a health center-delivered, educational intervention that improved infant growth in Trujillo, Peru: successes and challenges.

Process evaluation was used to examine the implementation of a randomized, controlled trial of an education intervention that improved infant growth in Trujillo, Peru. Health personnel delivered the multi-component intervention as part of usual care in the government health centers. Quantitative and qualitative methods were used to examine process indicators, which included the extent of delivery (dose), fidelity to intervention protocol, barriers to implementation and context. Results demonstrated that most intervention components were delivered at a level of 50-90% of expectations. Fidelity to intervention protocol, where measured, was lower (28-70% of expectations). However, when compared with existing nutrition education, as represented by the control centers, significant improvements were demonstrated. This included both improved delivery of existing educational activities as well as delivery of new intervention components to strengthen overall nutrition education. Barriers to, and facilitators of, implementation were explored with health personnel and helped to explain results. This study demonstrates the importance of examining actual versus planned implementation in order to improve our understanding of how interventions succeed. The information gained from this study will inform future evaluation designs, and lead to the development and implementation of more effective intervention programs for child health.

The cost-effectiveness of a child nutrition education programme in Peru.

This article reports impact and cost results from a health facility-based nutrition education programme targeting children less than 2 years of age in Trujillo, Peru. Key elements of the programme included participative complementary feeding demonstrations, growth monitoring sessions and an accreditation process. Data were collected from six intervention and six control health facilities to measure utilization and costs associated with the intervention. To calculate the unit costs of services, these costs are allocated using activity-based costing. To measure the effects of the intervention, 338 children were followed through household surveys at regular intervals from birth until the age of 18 months. The intervention had a clear positive impact both on the use of nutrition-related services and on children's growth outcomes. Children in the intervention areas made 17.6 visits to health facilities in the first 18 months of life, compared with 14.1 visits for children in the control areas (P < 0.001). This pattern holds true for all socioeconomic groups. The intervention prevented 11.1 cases of stunting per 100 children. In multivariate logistic regression analysis, children in the intervention were 0.33 times as likely to be stunted as the controls (P = 0.002). The marginal cost of the intervention - including external costs, training, health education materials and extra travel and equipment - is 6.12 US dollars per child reached and 55.16 US dollars per case of stunting prevented. The estimated marginal cost of the intervention per death averted is 1952 US dollars.

Process evaluation determines the pathway of success for a health center-delivered, nutrition education intervention for infants in Trujillo, Peru.

Process evaluation was used to explain the success of a randomized, controlled trial of an educational intervention to improve the feeding behaviors of caregivers and the nutritional status of infants in Trujillo, Peru. Health personnel delivered a multicomponent intervention within the environment of usual care at government health centers. We created a model of the expected intervention pathway to successful outcomes. Process data were then collected on health center implementation of the intervention and caregiver reception to it. Using multivariate models, we found that variables of health center implementation, caregiver exposure, and caregiver message recall were all significant determinants in the pathway leading to improved feeding behaviors. These outcomes were consistent with our original intervention model. Further support for our model arose from the differences in caregiver reception between intervention and control centers. Process data allowed us to characterize the pathway through which an effective nutrition intervention operated. This study underscores the importance of including process evaluation, which will lead to the development and implementation of more effective nutrition interventions.