Phillippa M. Cumberland

Neonatal Measles Immunity in Rural Kenya: The Influence of HIV and Placental Malaria Infections on Placental Transfer of Antibodies and Levels of Antibody in Maternal and Cord Serum Samples

INTRODUCTION Young infants are protected from measles infection by maternal measles antibodies. The level of these antibodies at birth depends on the level of antibodies in the mother and the extent of placental transfer. We investigated predictors of levels of measles antibodies in newborns in rural Kenya. METHODS A total of 747 paired maternal-cord serum samples (91 from human immunodeficiency virus [HIV]-infected and 656 from HIV-uninfected mothers) were tested for measles immunoglobulin G antibodies. Placental malaria infection was determined by biopsy. Data on pregnancy history, gestational age, and anthropometric and socioeconomic status were collected. RESULTS Infants born to HIV-infected mothers were more likely (odds ratio, 4.6 [95% confidence interval {CI}, 2.2-9.7]) to be seronegative and had 35.1% (95% CI, 9.8%-53.2%) lower levels of measles antibodies than did those born to HIV-uninfected mothers. Preterm delivery, early maternal age, and ethnic group were also associated with reduced levels of measles antibodies. There was little evidence that placental malaria infection was associated with levels of measles antibodies in newborns. CONCLUSION Our results suggest that maternal HIV infection may reduce levels of measles antibodies in newborns. Low levels of measles antibodies at birth render children susceptible to measles infection at an early age. This is of concern in sub-Saharan African countries, where not only is the prevalence of HIV high, but measles is the cause of much morbidity and mortality.

Increasing Prevalence of Myopia in Europe and the Impact of Education

Purpose To investigate whether myopia is becoming more common across Europe and explore whether increasing education levels, an important environmental risk factor for myopia, might explain any temporal trend. Design Meta-analysis of population-based, cross-sectional studies from the European Eye Epidemiology (E3) Consortium. Participants The E3 Consortium is a collaborative network of epidemiological studies of common eye diseases in adults across Europe. Refractive data were available for 61 946 participants from 15 population-based studies performed between 1990 and 2013; participants had a range of median ages from 44 to 78 years. Methods Noncycloplegic refraction, year of birth, and highest educational level achieved were obtained for all participants. Myopia was defined as a mean spherical equivalent ≤−0.75 diopters. A random-effects meta-analysis of age-specific myopia prevalence was performed, with sequential analyses stratified by year of birth and highest level of educational attainment. Main Outcome Measures Variation in age-specific myopia prevalence for differing years of birth and educational level. Results There was a significant cohort effect for increasing myopia prevalence across more recent birth decades; age-standardized myopia prevalence increased from 17.8% (95% confidence interval [CI], 17.6–18.1) to 23.5% (95% CI, 23.2–23.7) in those born between 1910 and 1939 compared with 1940 and 1979 (P = 0.03). Education was significantly associated with myopia; for those completing primary, secondary, and higher education, the age-standardized prevalences were 25.4% (CI, 25.0–25.8), 29.1% (CI, 28.8–29.5), and 36.6% (CI, 36.1–37.2), respectively. Although more recent birth cohorts were more educated, this did not fully explain the cohort effect. Compared with the reference risk of participants born in the 1920s with only primary education, higher education or being born in the 1960s doubled the myopia prevalence ratio–2.43 (CI, 1.26–4.17) and 2.62 (CI, 1.31–5.00), respectively—whereas individuals born in the 1960s and completing higher education had approximately 4 times the reference risk: a prevalence ratio of 3.76 (CI, 2.21–6.57). Conclusions Myopia is becoming more common in Europe; although education levels have increased and are associated with myopia, higher education seems to be an additive rather than explanatory factor. Increasing levels of myopia carry significant clinical and economic implications, with more people at risk of the sight-threatening complications associated with high myopia.

Genome-wide meta-analysis of myopia and hyperopia provides evidence for replication of 11 loci

Refractive error (RE) is a complex, multifactorial disorder characterized by a mismatch between the optical power of the eye and its axial length that causes object images to be focused off the retina. The two major subtypes of RE are myopia (nearsightedness) and hyperopia (farsightedness), which represent opposite ends of the distribution of the quantitative measure of spherical refraction. We performed a fixed effects meta-analysis of genome-wide association results of myopia and hyperopia from 9 studies of European-derived populations: AREDS, KORA, FES, OGP-Talana, MESA, RSI, RSII, RSIII and ERF. One genome-wide significant region was observed for myopia, corresponding to a previously identified myopia locus on 8q12 (p = 1.25×10−8), which has been reported by Kiefer et al. as significantly associated with myopia age at onset and Verhoeven et al. as significantly associated to mean spherical-equivalent (MSE) refractive error. We observed two genome-wide significant associations with hyperopia. These regions overlapped with loci on 15q14 (minimum p value = 9.11×10−11) and 8q12 (minimum p value 1.82×10−11) previously reported for MSE and myopia age at onset. We also used an intermarker linkage- disequilibrium-based method for calculating the effective number of tests in targeted regional replication analyses. We analyzed myopia (which represents the closest phenotype in our data to the one used by Kiefer et al.) and showed replication of 10 additional loci associated with myopia previously reported by Kiefer et al. This is the first replication of these loci using myopia as the trait under analysis. “Replication-level” association was also seen between hyperopia and 12 of Kiefer et al.s published loci. For the loci that show evidence of association to both myopia and hyperopia, the estimated effect of the risk alleles were in opposite directions for the two traits. This suggests that these loci are important contributors to variation of refractive error across the distribution.

Does amblyopia affect educational, health, and social outcomes? Findings from 1958 British birth cohort

Abstract Objective To determine any association of amblyopia with diverse educational, health, and social outcomes in order to inform current debate about population screening for this condition. Design, setting, and participants Comparison of 8432 people with normal vision in each eye with 429 (4.8%) people with amblyopia (childhood unilateral reduced acuity when tested with correction and unaccounted for by eye disease) from the 1958 British birth cohort, with respect to subsequent health and social functioning. Results No functionally or clinically significant differences existed between people with and without amblyopia in educational outcomes, behavioural difficulties or social maladjustment, participation in social activities, unintended injuries (school, workplace, or road traffic accidents as driver), general or mental health and mortality, paid employment, or occupation based social class trajectories. Conclusions It may be difficult to distinguish, at population level, between the lives of people with amblyopia and those without, in terms of several important outcomes. A pressing need exists for further concerted research on what it means to have amblyopia and, specifically, how this varies with severity and how it changes with treatment, so that screening programmes can best serve those who have the most to gain from early identification.

Outcomes of childhood epilepsy at age 33 years: A population-based birth-cohort study

Purpose:  There is uncertainty about health and socioeconomic outcomes of children with epilepsy, knowledge of adult outcomes, and factors associated with adverse outcomes are essential to guide prognosis, improve management, and determine appropriate allocation of resources.

Visual Function in Working-Age Adults: Early Life Influences and Associations with Health and Social Outcomes

PURPOSE To investigate how visual function in mid-adult life is associated with health and social outcomes and, using life-course epidemiology, whether it is influenced by early life biological and social factors. DESIGN Population-based cohort study. PARTICIPANTS Nine thousand three hundred thirty members of the 1958 British birth cohort at age 44 or 45 years. METHODS Distance, near, and stereo vision were assessed as part of a broader biomedical examination. Logistic, multinomial, and proportional odds ordinal logistic regression were used, as appropriate, to assess the association between these vision functions and both key early life influences and health and social outcomes in mid-adult life. MAIN OUTCOME MEASURES Distance, near, and stereo acuities and health and social outcomes. RESULTS In mid-adult life, vision function (across the full spectrum of both type and level of function) is associated with unemployment resulting from permanent sickness, lower socioeconomic status, and poorer general health (for example, for blindness; odds ratios were 2.5, 2.6, and 1.2, respectively). Also, impaired visual functions in mid-adult life are associated with a low birthweight, being small for gestational age, maternal smoking in pregnancy, and markers of socioeconomic deprivation in childhood (for example, for impaired distance acuity; odds ratios were 1.4, 1.3, 1.02, and 1.1, respectively). CONCLUSIONS Although relatively uncommon in working-age adults, impaired vision can have important adverse consequences, which highlights the value of investigating visual function in the broader context of health and social functioning. In addition, visual function in adult life may be influenced directly by key prenatal and childhood biological and social determinants of general health. Thus, application of life-course epidemiology to complex chronic ophthalmic diseases of adult life such as glaucoma or macular degeneration is likely to prove valuable in elucidating whether and how biological, social, and lifestyle factors contribute to the cause.

Evaluation of a measles vaccine campaign in Ethiopia using oral-fluid antibody surveys

We undertook a study to demonstrate the potential contribution of oral-fluid (OF) antibody prevalence surveys in evaluating measles vaccine campaigns. In Asela town, southern Ethiopia, oral fluids were collected from 1928 children aged 9 months to 5 years attending for campaign immunization in December 1999 and 6 months later, from 745 individuals aged 9 months to 19 years, in the same location. Measles antibody status was determined by microimmune measles specific IgG enzyme immunoassay (EIA). Antibody prevalence was estimated at 48% in children attending for vaccination (pre-campaign), and 85% post-campaign in the comparable age group. The estimated reduction in the susceptible proportion was 75%. In older children the proportion antibody negative post-campaign was 28% in 7-9 year olds, and 13% in 10-14 year olds levels of susceptibility which raise concern over continued measles transmission. This is the first evaluation of a measles vaccine campaign based on oral-fluid seroprevalence surveys and it demonstrates the merit of oral-fluid surveys in informing health authorities about vaccination strategy refinement.

The improving outcomes in intermittent exotropia study: outcomes at 2 years after diagnosis in an observational cohort

BackgroundThe purpose of this study was to investigate current patterns of management and outcomes of intermittent distance exotropia [X(T)] in the UK.MethodsThis was an observational cohort study which recruited 460 children aged < 12 years with previously untreated X(T). Eligible subjects were enrolled from 26 UK hospital ophthalmology clinics between May 2005 and December 2006. Over a 2-year period of follow-up, clinical data were prospectively recorded at standard intervals from enrolment. Data collected included angle, near stereoacuity, visual acuity, control of X(T) measured with the Newcastle Control Score (NCS), and treatment. The main outcome measures were change in clinical outcomes (angle, stereoacuity, visual acuity and NCS) in treated and untreated X(T), 2 years from enrolment (or, where applicable, 6 months after surgery). Change over time was tested using the chi-square test for categorical, Wilcoxon test for non-parametric and paired-samples t-test for parametric data.ResultsAt follow-up, data were available for 371 children (81% of the original cohort). Of these: 53% (195) had no treatment; 17% (63) had treatment for reduced visual acuity only (pure refractive error and amblyopia); 13% (50) had non surgical treatment for control (spectacle lenses, occlusion, prisms, exercises) and 17% (63) had surgery. Only 0.5% (2/371) children developed constant exotropia. The surgically treated group was the only group with clinically significant improvements in angle or NCS. However, 8% (5) of those treated surgically required second procedures for overcorrection within 6 months of the initial procedure and at 6-month follow-up 21% (13) were overcorrected.ConclusionsMany children in the UK with X(T) receive active monitoring only. Deterioration to constant exotropia, with or without treatment, is rare. Surgery appears effective in improving angle of X(T) and NCS, but rates of overcorrection are high.

Inferring myopia over the lifecourse from uncorrected distance visual acuity in childhood

Aim: To report the usefulness of uncorrected distance visual acuity (DVA) at 16 years to “screen” for myopia status and to assess the lifetime risk of myopia, based on a national birth cohort. Methods: 1867 members of the 1958 British birth cohort for whom there were data on acuity at 16 years had autorefraction, as part of a biomedical survey, at 45 years. Reduced uncorrected DVA at age 16 years (6/12 or worse in both eyes) was compared with adult refraction (spherical equivalent). Results: Only a quarter of individuals in the population studied who had developed myopia by 45 years of age had reduced acuity at 16 years of age. Notably, half of all adults with moderate myopia (−2.99 to −5.99) and 31% (11/35) with severe myopia (⩾−6) had good uncorrected DVA in both eyes at 16 years of age. Thus, sensitivities were low, ranging from 16% for all myopia (cut-off point spherical equivalent −0.5) to 69% for severe myopia (cut-off point spherical equivalent −6). However, a high (91%) lifetime probability of primary myopia (spherical equivalent ⩾−0.5) given a reduced uncorrected DVA at 16 years was found. Conclusion: In this population, reduced uncorrected DVA in childhood is an inaccurate and inappropriate intermediate “phenotype” for capturing adult myopia status. However, our findings support assessment of DVA in secondary school children as an effective method of identifying refractive error (both myopia and hypermetropia).

Risk factors for active trachoma and Chlamydia trachomatis infection in rural Ethiopia after mass treatment with azithromycin

Objectives  To investigate risk factors for ocular Chlamydia trachomatis infection and active trachoma, comparing communities receiving or not receiving an intervention programme of community‐wide azithromycin treatment and health education.