Determinants of high residual post-PCV13 pneumococcal vaccine-type carriage in Blantyre, Malawi:a modelling study

Background In November 2011, Malawi introduced the 13-valent pneumococcal conjugate vaccine (PCV13) into the routine infant schedule. Four to 7 years after introduction (2015–2018), rolling prospective nasopharyngeal carriage surveys were performed in the city of Blantyre. Carriage of Streptococcus pneumoniae vaccine serotypes (VT) remained higher than reported in high-income countries, and impact was asymmetric across age groups. Methods A dynamic transmission model was fit to survey data using a Bayesian Markov-chain Monte Carlo approach, to obtain insights into the determinants of post-PCV13 age-specific VT carriage. Results Accumulation of naturally acquired immunity with age and age-specific transmission potential were both key to reproducing the observed data. VT carriage reduction peaked sequentially over time, earlier in younger and later in older age groups. Estimated vaccine efficacy (protection against carriage) was 66.87% (95% CI 50.49–82.26%), similar to previous estimates. Ten-year projected vaccine impact (VT carriage reduction) among 0–9 years old was lower than observed in other settings, at 76.23% (CI 95% 68.02–81.96%), with sensitivity analyses demonstrating this to be mainly driven by a high local force of infection. Conclusions There are both vaccine-related and host-related determinants of post-PCV13 pneumococcal VT transmission in Blantyre with vaccine impact determined by an age-specific, local force of infection. These findings are likely to be generalisable to other Sub-Saharan African countries in which PCV impact on carriage (and therefore herd protection) has been lower than desired, and have implications for the interpretation of post-PCV carriage studies and future vaccination programs.</p

Out‐of‐home care placements of children and adolescents born preterm:a register‐based cohort study

Abstract Background: Preterm birth predisposes to child protection action in the form out‐of‐home care. The impact of the degree of preterm birth on the likelihood for OHC placement(s) and their timing is unknown. Methods: This population‐based register‐linkage study assessed the likelihood of OHC placement in different gestational age groups using multivariable Cox regression models. All 193 033 traceable singleton (8324 preterm, 4.3%) liveborn in Finland (January 1987‐September 1990), as the first index child of each mother within the cohort period, were followed up until their 18th birthday. Results: A total of 6562 children (3.4%) experienced OHC. In comparison with full‐term children (39‐41 weeks), those born at 23‐33 completed weeks were predisposed to OHC (hazard ratio [HR] 2.11, 95% confidence interval [CI] 1.74, 2.56). For those born late preterm (34‐36 weeks) and early term (37‐38 weeks), the HR were 1.54 (95% CI 1.37, 1.73) and 1.19 (95% CI 1.12, 1.26), respectively. Adjustment for parental and child characteristics attenuated the HRs: 23‐33 weeks: 1.31 (95% CI 1.07, 1.59), 34‐36 weeks: 1.17 (95% CI 1.04, 1.31), and 37‐38 weeks: 1.08 (95% CI 1.02, 1.16). However, the adjusted HRs for first OHC entries at 0‐5 years of age were higher: 23‐33 weeks 2.29 (95% CI 1.72, 3.05), 34‐36 weeks 1.76 (95% CI 1.46, 2.13), and 37‐38 weeks 1.40 (95% CI 1.25, 1.56). Among those born preterm or early term, in comparison with their term born peers, no excess risk for OHC was seen after 5 years. Conclusions: A dose‐response relationship exists between the level of preterm birth and OHC placement risk. OHC placements are more common among early and late preterm, and early term children, compared with those born full term, and occur at younger age. Perinatal and postnatal adverse circumstances appear to explain the phenomenon only partly

Body composition among Malawian young adolescents:cross-validating predictive equations for bioelectric impedance analysis using deuterium dilution method

Abstract Background: Body composition can be measured by several methods, each with specific benefits and disadvantages. Bioelectric impedance offers a favorable balance between accuracy, cost and ease of measurement in a range of settings. In this method, bioelectric measurements are converted to body composition measurements by prediction equations specific to age, population and bioimpedance device. Few prediction equations exist for populations in low-resource settings. We formed a prediction equation for total body water in Malawian adolescents using deuterium dilution as reference. Methods: We studied 86 boys and 92 girls participating in the 11-14-year follow-up of the Lungwena Antenatal Intervention Study, a randomized trial of presumptive infection treatment among pregnant women. We measured body composition by Seca m515 bioimpedance analyser. Participants ingested a weight-standardized dose of deuterium oxide, after which we collected saliva at baseline, at 3 and 4 h post-ingestion, measured deuterium concentration using Fourier-transform infrared spectroscopy and calculated total body water. We formed predictive equations for total body water using anthropometrics plus resistance and reactance at a range of frequencies, applying multiple regression and repeated cross-validation in model building and in prediction error estimation. Results: The best predictive model for percentage total body water (TBW %) was 100*(1.11373 + 0.0037049*height (cm)²/resistance(Ω) at 50 kHz– 0.25778*height(m)– 0.01812*BMI(kg/m²)– 0.02614*female sex). Calculation of absolute TBW (kg) by multiplying TBW (%) with body weight had better predictive power than a model directly constructed to predict absolute total body water (kg). This model explained 96.4% of variance in TBW (kg) and had a mean prediction error of 0.691 kg. Mean bias was 0.01 kg (95% limits of agreement -1.34, 1.36) for boys and -0.01 kg (1.41, 1.38) for girls. Conclusions: Our equation provides an accurate, cost-effective and participant-friendly body composition prediction method among adolescents in clinic-based field studies in rural Africa, where electricity is available

Preterm birth and subsequent timing of pubertal growth, menarche, and voice break

Abstract Background: We evaluated pubertal growth and pubertal timing of participants born preterm compared to those born at term. Methods: In the ESTER Preterm Birth Study, we collected growth data and measured final height of men/women born very or moderately preterm (&lt;34 gestational weeks, n = 52/55), late preterm (34–&lt;37 weeks, 94/106), and term (≥37 weeks, 131/151), resulting in median 9 measurements at ≥6 years. Timing of menarche or voice break was self-reported. Peak height velocity (PHV, cm/year) and age at PHV (years) were compared with SuperImposition by Translation And Rotation (SITAR) model (sexes separately). Results: Age at PHV (years) and PHV (cm/year) were similar in all gestational age groups. Compared to term controls, insignificant differences in age at PHV were 0.1 (95% CI: −0.2 to 0.4) years/0.2 (−0.1 to 0.4) for very or moderately/late preterm born men and −0.0 (−0.3 to 0.3)/−0.0 (−0.3 to 0.2) for women, respectively. Being born small for gestational age was not associated with pubertal growth. Age at menarche or voice break was similar in all the gestational age groups. Conclusions: Timing of pubertal growth and age at menarche or voice break were similar in participants born preterm and at term

Serum ceramides in early pregnancy as predictors of gestational diabetes

Abstract Ceramides contribute to the development of type 2 diabetes but it is uncertain whether they predict gestational diabetes (GDM). In this multicentre case–control study including 1040 women with GDM and 958 non-diabetic controls, early pregnancy (mean 10.7 gestational weeks) concentrations of four ceramides—Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0) and Cer(d18:1/24:1)—were determined by a validated mass-spectrometric method from biobanked serum samples. Traditional lipids including total cholesterol, LDL, HDL and triglycerides were measured. Logistic and linear regression and the LASSO logistic regression were used to analyse lipids and clinical risk factors in the prediction of GDM. The concentrations of four targeted ceramides and total cholesterol, LDL and triglycerides were higher and HDL was lower among women with subsequent GDM than among controls. After adjustments, Cer(d18:1/24:0), triglycerides and LDL were independent predictors of GDM, women in their highest quartile had 1.44-fold (95% CI 1.07–1.95), 2.17-fold (95% CI 1.57–3.00) and 1.63-fold (95% CI 1.19–2.24) odds for GDM when compared to their lowest quartiles, respectively. In the LASSO regression modelling ceramides did not appear to markedly improve the predictive performance for GDM alongside with clinical risk factors and triglycerides. However, their adverse alterations highlight the extent of metabolic disturbances involved in GDM

Gestational age, parent education, and education in adulthood

Abstract Background: Adults born preterm (&lt;37 weeks) have lower educational attainment than those born term. Whether this relationship is modified by family factors such as socioeconomic background is, however, less well known. We investigated whether the relationship between gestational age and educational attainment in adulthood differed according to parents’ educational level in 4 Nordic countries. Methods: This register-based cohort study included singletons born alive from 1987 up to 1992 in Denmark, Finland, Norway, and Sweden. In each study population, we investigated effect modification by parents’ educational level (low, intermediate, high) on the association between gestational age at birth (25–44 completed weeks) and low educational attainment at 25 years (not having completed upper secondary education) using general estimation equations logistic regressions. Results: A total of 4.3%, 4.0%, 4.8%, and 5.0% singletons were born preterm in the Danish (n = 331 448), Finnish (n = 220 095), Norwegian (n = 292 840), and Swedish (n = 513 975) populations, respectively. In all countries, both lower gestational age and lower parental educational level contributed additively to low educational attainment. For example, in Denmark, the relative risk of low educational attainment was 1.84 (95% confidence interval 1.44 to 2.26) in adults born at 28 to 31 weeks whose parents had high educational level and 5.25 (95% confidence interval 4.53 to 6.02) in adults born at 28 to 31 weeks whose parents had low educational level, compared with a reference group born at 39 to 41 weeks with high parental educational level. Conclusions: Although higher parental education level was associated with higher educational attainment for all gestational ages, parental education did not mitigate the educational disadvantages of shorter gestational age

Pneumococcal Transmission and Disease In Silico: A Microsimulation Model of the Indirect Effects of Vaccination

BACKGROUND: The degree and time frame of indirect effects of vaccination (serotype replacement and herd immunity) are key determinants in assessing the net effectiveness of vaccination with pneumococcal conjugate vaccines (PCV) in control of pneumococcal disease. Using modelling, we aimed to quantify these effects and their dependence on coverage of vaccination and the vaccine's efficacy against susceptibility to pneumococcal carriage. METHODS AND FINDINGS: We constructed an individual-based simulation model that explores the effects of large-scale PCV programmes and applied it in a developed country setting (Finland). A population structure with transmission of carriage taking place within relevant mixing groups (families, day care groups, schools and neighbourhoods) was considered in order to properly assess the dependency of herd immunity on coverage of vaccination and vaccine efficacy against carriage. Issues regarding potential serotype replacement were addressed by employing a novel competition structure between multiple pneumococcal serotypes. Model parameters were calibrated from pre-vaccination data about the age-specific carriage prevalence and serotype distribution. The model predicts that elimination of vaccine-type carriage and disease among those vaccinated and, due to a substantial herd effect, also among the general population takes place within 5-10 years since the onset of a PCV programme with high (90%) coverage of vaccination and moderate (50%) vaccine efficacy against acquisition of carriage. A near-complete replacement of vaccine-type carriage by non-vaccine-type carriage occurs within the same time frame. CONCLUSIONS: The changed patterns in pneumococcal carriage after PCV vaccination predicted by the model are unequivocal. The overall effect on disease incidence depends crucially on the magnitude of age- and serotype-specific case-to-carrier ratios of the remaining serotypes relative to those of the vaccine types. Thus the availability of reliable data on the incidence of both pneumococcal carriage and disease is essential in assessing the net effectiveness of PCV vaccination in a given epidemiological setting