Mary E. Penny

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.).

Effectiveness of an educational intervention delivered through the health services to improve nutrition in young children: a cluster-randomised controlled trial

BACKGROUND Malnutrition is the underlying cause of half of child mortality. Many programmes attempt to remedy this issue but there is a lack of evidence on effective ways to decrease child malnutrition. METHODS We did a cluster-randomised trial of an educational intervention in a poor periurban area (ie, shanty town) of Peru. Guided by formative research, the intervention aimed to enhance the quality and coverage of existing nutrition education and to introduce an accreditation system in six government health facilities compared with six control facilities. The primary outcome measure was growth that was measured by weight, length, and Z scores for weight-for-age and length-for-age at age 18 months. Main secondary outcomes were the percentage of children receiving recommended feeding practices and the 24-h dietary intake of energy, iron, and zinc from complementary food at ages 6, 9, 12, and 18 months. Analysis was by intention to treat. FINDINGS We enrolled a birth cohort of 187 infants from the catchment areas of intervention centres and 190 from control areas. Caregivers in intervention areas were more likely to report receiving nutrition advice from the health service than were caregivers in control health facilities (16 [52%] of 31 vs 9 [24%] of 37, p=0.02). At 6 months more babies in intervention areas were fed nutrient-dense thick foods at lunch (a recommended complementary feeding practice) than were controls (48 [31%] of 157 vs 29 [20%] of 147; difference between groups 19 [11%], p=0.03). Fewer children in intervention areas failed to meet dietary requirements for energy (8 months: 30 [18%] of 170 vs 45 [27%] of 167, p=0.04; 12 months: 64 [38%] of 168 vs 82 [49%] of 167, p=0.043), iron (8 months: 155 [91%] of 170 vs 161 [96%] of 167, 9 months: 152 [93%] of 163 vs 165 [99%] of 166, p=0.047), and zinc (9 months: 125 [77%] of 163 vs 145 [87%] of 166, p=0.012) than did controls. Children in control areas were more likely to have stunted growth (ie, length for age less than 2 SD below the reference population median) at 18 months than children in intervention groups (26 [16%] of 165 vs 8 [5%] of 171; adjusted odds ratio 3.04 [95% CI 1.21-7.64]). Adjusted mean changes in weight gain, length gain, and Z scores were all significantly better in the intervention area than in the control area. INTERPRETATION Improvement of nutrition education delivered through health services can decrease the prevalence of stunted growth in childhood in areas where access to food is not a limiting factor.

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.

Children Who Recover from Early Stunting and Children Who Are Not Stunted Demonstrate Similar Levels of Cognition

Stunting is associated with adverse cognitive development in childhood and adolescence, fewer years of schooling, decreased productivity, and reduced adult stature. Recovery from early stunting is possible; however, few studies explore whether those who demonstrate linear catch-up growth experience long-term cognitive deficits. Using longitudinal data on 1674 Peruvian children from the Young Lives study, we identified factors associated with catch-up growth and assessed whether children who displayed catch-up growth have significantly lower cognition than children who were not stunted during infancy and childhood. Based on anthropometric data for children 6-18 mo of age and again for the same children when they were 4.5-6 y of age, we categorized participants as not stunted, stunted in infancy but not childhood (catch-up), stunted in childhood, and stunted in infancy and childhood. Children who had grandparents in the home, had less severe stunting in infancy, and had taller mothers were more likely to demonstrate catch-up growth by round 2. Children who experienced catch-up growth had verbal vocabulary and quantitative test scores that did not differ from children who were not stunted (P = 0.6 and P = 0.7, respectively). Those stunted in childhood as well as those stunted in infancy and childhood scored significantly lower on both assessments than children who were not stunted. Based on findings from this study, policy makers and program planners should consider redoubling efforts to prevent stunting and promote catch-up growth over the first few years of life as a way of improving childrens physical and intellectual development.

Randomized, community-based trial of the effect of zinc supplementation, with and without other micronutrients, on the duration of persistent childhood diarrhea in Lima, Peru

OBJECTIVE To determine whether supplemental zinc, with or without additional micronutrients, affects the severity and duration of persistent childhood diarrhea and the rate of nutritional recovery. DESIGN The study was a community-based, double-blind, randomized trial implemented in a shanty town in Lima, Peru. Children aged 6 to 36 months with persistent (>/=14 days) diarrhea received daily, for 2 weeks, a placebo (group P, n = 136) or a supplement of 20 mg of zinc, either with (group Z+VM, n = 137) or without (group Z, n = 139) additional vitamins and minerals. Symptoms of illness were recorded daily, and biochemical and anthropometric assessments were completed at baseline and on day 15. RESULTS The treatment groups were similar at baseline with regard to the characteristics of the presenting episode, anthropometric data, and plasma zinc concentration. The children consumed, on average, 95% (group P), 94% (group Z), or 88% (group Z+VM) of the supplement (P <.001). The plasma zinc concentration did not change significantly from baseline to day 15 in group P (4 microg/dL) but increased by 38 microg/dL in group Z and 14 microg/dL in group Z+VM. The median duration of diarrhea after starting treatment was 1 day; among children who continued to have diarrhea, there was a significant effect of treatment on diarrheal duration (P =.04, analysis of covariance). Specifically, the duration of illness was significantly reduced by 28% in children in group Z (P =.01) and by 33% in girls in group Z+VM (P =.04). There were no differences in the severity of the episode by treatment group. CONCLUSION There was a significant reduction in the duration of persistent diarrhea in selected subgroups of zinc-supplemented ambulatory patients in this population.

Postinfancy growth, schooling, and cognitive achievement: Young Lives

Background: Early life growth failure and resulting cognitive deficits are often assumed to be very difficult to reverse after infancy. Objective: We used data from Young Lives, which is an observational cohort of 8062 children in Ethiopia, India, Peru, and Vietnam, to determine whether changes in growth after infancy are associated with schooling and cognitive achievement at age 8 y. Design: We represented the growth by height-for-age z score at 1 y [HAZ(1)] and height-for-age z score at 8 y that was not predicted by the HAZ(1). We also characterized growth as recovered (stunted at age 1 y and not at age 8 y), faltered (not stunted at age 1 y and stunted at age 8 y), persistently stunted (stunted at ages 1 and 8 y), or never stunted (not stunted at ages 1 and 8 y). Outcome measures were assessed at age 8 y. Results: The HAZ(1) was inversely associated with overage for grade and positively associated with mathematics achievement, reading comprehension, and receptive vocabulary. Unpredicted growth from 1 to 8 y of age was also inversely associated with overage for grade (OR range across countries: 0.80–0.84) and positively associated with mathematics achievement (effect-size range: 0.05–0.10), reading comprehension (0.02–0.10), and receptive vocabulary (0.04–0.08). Children who recovered in linear growth had better outcomes than did children who were persistently stunted but were not generally different from children who experienced growth faltering. Conclusions: Improvements in child growth after early faltering might have significant benefits on schooling and cognitive achievement. Hence, although early interventions remain critical, interventions to improve the nutrition of preprimary and early primary school–age children also merit consideration.

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.

Respiratory symptoms, asthma, exercise test spirometry, and atopy in schoolchildren from a Lima shanty town

BACKGROUND Little is known about the associations between symptoms of asthma, pulmonary function tests, and atopy in developing countries. While asthma in children is often associated with atopy, some studies of wheezing illness have found little or no association, leading to suggestions that there are subgroups of wheezing illness. The ISAAC study recently reported that the prevalence of reported asthma symptoms in Lima, Peru was among the highest in the world, but did not report on the atopic status of the subjects. METHODS A cross sectional survey was conducted of children aged 8–10 years who had previously participated in a cohort study of respiratory and diarrhoeal illnesses in infancy. Questionnaires were administered asking about respiratory symptoms and asthma diagnoses, pulmonary function tests were performed before and after exercise on a treadmill, and atopy was determined from skin prick tests and specific serum IgE levels. RESULTS A total of 793 children participated in the survey. The prevalence of asthma related symptoms in the last 12 months was 23.2%, but only 3.8% of children reported a recent asthma attack. The mean differences in pretest percentage predicted forced expiratory volume in one second (FEV1) were 8.1% (95% CI 2.4 to 13.8) between children who did and did not report an asthma attack in the last 12 months, and 5.3% (95% CI 2.8 to 7.9) in children who did and did not report respiratory symptoms. The corresponding differences in mean percentage fall in FEV1 after exercise were 3.1% (95% CI –1 to 7.1) and 5.1% (95% CI 3.4 to 6.8). Recent asthma or respiratory symptoms were not associated with atopy in this population (odds ratios 1.29 (95% CI 0.56 to 2.97) and 0.91 (95% CI 0.61 to 1.37), respectively). CONCLUSIONS Most asthma in these children was unrecognised and mild. Asthma and asthma symptoms in this population do not seem to be related to atopy.

Impact of early and concurrent stunting on cognition

Undernutrition is associated with poor cognitive development, late entry into school, decreased years of schooling, reduced productivity and smaller adult stature. We use longitudinal data from 1674 Peruvian children participating in the Young Lives study to assess the relative impact of early stunting (stunted at 6-18 months of age) and concurrent stunting (stunted at 4.5-6 years of age) on cognitive ability. Anthropometric data were longitudinally collected for children at 6-18 months of age and 4.5-6 years of age at which time verbal and quantitative ability were also assessed. We estimate that an increase in concurrent height-for-age z-scores (HAZ) by one standard deviation was associated with an increase in a childs score on the Peabody Picture Vocabulary Test (PPVT) by 2.35 points [confidence interval (CI): 1.55-3.15] and a 0.16 point increase on the cognitive development assessment (CDA) (CI: 0.05-0.27). Furthermore, we report that the estimate for concurrent HAZ and PPVT is significantly higher than the estimate for early stunting and PPVT. We found no significant difference between early and concurrent estimates for HAZ and CDA. Children from older mothers, children whose mothers had higher education levels, children living in urban areas, children who attended pre-school, children with fewer siblings and children from wealthier backgrounds scored higher on both assessments. Cognitive skills of children entering school were associated with early stunting but the strongest association was found with concurrent stunting suggesting that interventions preventing linear growth faltering should not only focus on the under 2s but include children up to 5 years of age.

Cohort Profile: The Young Lives Study

Young Lives is an international longitudinal study investigating the changing nature of childhood poverty in four low-income countries [Ethiopia, India (Andhra Pradesh), Peru and Vietnam] over a 15-year period. In each country, the cohort is comprised of ≈ 2000 children aged between 6 and 18 months and up to 1000 children aged between 7 and 8 years, recruited in 2002 and sampled from 20 sentinel sites. The first survey data collection from primary caregivers and older children took place in 2002, the second in 2006-07 and the third in 2009-10. Data on the community contexts were collected to complement the household surveys. To elaborate and extend the quantitative data, longitudinal qualitative research with a subgroup of the children was carried out in 2007, 2008 and 2010-11. Topic areas covered included nutrition, health and well-being, cognitive and physical development, health behaviours and education, as well as the social, demographic and economic status of the household. Survey data from the study are archived in the International Section of the UK Public Data Archive.