Sugnet Gardner-Lubbe

Aetiology of childhood pneumonia in a well vaccinated South African birth cohort: a nested case-control study of the Drakenstein Child Health Study

Summary Background Pneumonia is a leading cause of mortality and morbidity in children globally. The cause of pneumonia after introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) has not been well studied in low-income and middle-income countries, and most data are from cross-sectional studies of children admitted to hospital. We aimed to longitudinally investigate the incidence and causes of childhood pneumonia in a South African birth cohort. Methods We did a nested case-control study of children in the Drakenstein Child Health Study who developed pneumonia from May 29, 2012, to Dec 1, 2014. Children received immunisations including acellular pertussis vaccine and PCV13. A nested subgroup had nasopharyngeal swabs collected every 2 weeks throughout infancy. We identified pneumonia episodes and collected blood, nasopharyngeal swabs, and induced sputum specimens. We used multiplex real-time PCR to detect pathogens in nasopharyngeal swabs and induced sputum of pneumonia cases and in nasopharyngeal swabs of age-matched and site-matched controls. To show associations between organisms and pneumonia we used conditional logistic regression; results are presented as odds ratios (ORs) with 95% CIs. Findings 314 pneumonia cases occurred (incidence of 0·27 episodes per child-year, 95% CI 0·24–0·31; median age 5 months [IQR 3–9]) in 967 children during 1145 child-years of follow-up. 60 (21%) cases of pneumonia were severe (incidence 0·05 episodes per child-year [95% CI 0·04–0·07]) with a case fatality ratio of 1% (three deaths). A median of five organisms (IQR 4–6) were detected in cases and controls with nasopharyngeal swabs, and a median of six organisms (4–7) recorded in induced sputum (p=0·48 compared with nasopharyngeal swabs). Bordetella pertussis (OR 11·08, 95% CI 1·33–92·54), respiratory syncytial virus (8·05, 4·21–15·38), or influenza virus (4·13, 2·06–8·26) were most strongly associated with pneumonia; bocavirus, adenovirus, parainfluenza virus, Haemophilus influenzae, and cytomegalovirus were also associated with pneumonia. In cases, testing of induced sputum in addition to nasopharyngeal swabs provided incremental yield for detection of B pertussis and several viruses. Interpretation Pneumonia remains common in this highly vaccinated population. Respiratory syncytial virus was the most frequently detected pathogen associated with pneumonia; influenza virus and B pertussis were also strongly associated with pneumonia. Testing of induced sputum increases the yield for detection of several organisms. New vaccines and strategies are needed to address the burden of childhood pneumonia. Funding Bill & Melinda Gates Foundation, Medical Research Council South Africa, National Research Foundation South Africa, National Institute of Health, and H3Africa.

The BokSmart intervention programme is associated with improvements in injury prevention behaviours of rugby union players: an ecological cross-sectional study

Background/aim Participants of rugby union (‘rugby’) have an above-average risk of injury compared with other popular sports. Thus, BokSmart, a nationwide injury prevention programme for rugby, was introduced in South Africa in 2009. Improvements in injury-preventing behaviour of players are critical to the success of an intervention. The aim of this study was to assess whether BokSmart has been associated with improvements in rugby player behaviour. Methods An anonymous knowledge, attitude and self-reported behaviour questionnaire was completed by junior (under-18) and senior (adult) tournament players who attended merit-based tournaments (2008–2012). The questionnaire was completed by 2279 junior players (99% of total estimated population) from 111 teams and 1642 senior players (96% of population) from 81 teams. A generalised linear model assessed behavioural changes over this time period. Results Nine (50%) of the behaviours improved significantly (p<0.005) between 2008 and 2012 and the remaining behaviours remained unchanged. Improved behaviours included the targeted, catastrophic injury-preventing behaviours of the intervention: practising of tackling (adjusted overall improvement in odds: 56%) and scrummaging, in forwards only (58%), techniques. Other behaviours that improved significantly were postinjury compression and elevation as well as alcohol avoidance, mouthguard use (training and matches) and cooling down (training and matches). Practising of safe rucking techniques; warming up before training/matches; ice use; heat, massage and alcohol avoidance postinjury; and preseason and off-season conditioning remained unchanged. Conclusions BokSmart is associated with improvements in targeted injury-preventing behaviours in players. Future research should ascertain whether self-reported behaviours reflect actual behaviour and whether the observed improvements translate into changes in injury rates.

Visualisation of quadratic discriminant analysis and its application in exploration of microbial interactions

BackgroundWhen comparing diseased and non-diseased patients in order to discriminate between the aspects associated with the specific disease, it is often observed that the diseased patients have more variability than the non-diseased patients. In such cases Quadratic discriminant analysis is required which is based on the estimation of different covariance structures for the different groups. Having different covariance matrices means the Canonical variate transformation cannot be used to obtain a visual representation of the discrimination and group separation.ResultsIn this paper an alternative method is proposed: combining the different transformations for the different groups into a single representation of the sample points with classification regions. In order to associate the differences in variables with group discrimination, a biplot is produced which include information on the variables, samples and their relationship.

Spline-based nonlinear biplots

Biplots are helpful tools to establish the relations between samples and variables in a single plot. Most biplots use a projection interpretation of sample points onto linear lines representing variables. These lines can have marker points to make it easy to find the reconstructed value of the sample point on that variable. For classical multivariate techniques such as principal components analysis, such linear biplots are well established. Other visualization techniques for dimension reduction, such as multidimensional scaling, focus on an often nonlinear mapping in a low dimensional space with emphasis on the representation of the samples. In such cases, the linear biplot can be too restrictive to properly describe the relations between the samples and the variables. In this paper, we propose a simple nonlinear biplot that represents the marker points of a variable on a curved line that is governed by splines. Its main attraction is its simplicity of interpretation: the reconstructed value of a sample point on a variable is the value of the closest marker point on the smooth curved line representing the variable. The proposed spline-based biplot can never lead to a worse overall sample fit of the variable as it contains the linear biplot as a special case.

The Canonical Analysis of Distance

Canonical Variate Analysis (CVA) is one of the most useful of multivariate methods. It is concerned with separating between and within group variation among N samples from K populations with respect to p measured variables. Mahalanobis distance between the K group means can be represented as points in a (K - 1) dimensional space and approximated in a smaller space, with the variables shown as calibrated biplot axes. Within group variation may also be shown, together with circular confidence regions and other convex prediction regions, which may be used to discriminate new samples. This type of representation extends to what we term Analysis of Distance (AoD), whenever a Euclidean inter-sample distance is defined. Although the N × N distance matrix of the samples, which may be large, is required, eigenvalue calculations are needed only for the much smaller K × K matrix of distances between group centroids. All the ancillary information that is attached to a CVA analysis is available in an AoD analysis. We outline the theory and the R programs we developed to implement AoD by presenting two examples.

The analysis of distance of grouped data with categorical variables

We use generalised biplots to develop the important special case of (i) when all variables are categorical and (ii) the samples fall into K recognised groups. We term this Categorical Canonical Variate Analysis (CatCVA), because it has similar characteristics to Raos Canonical Variate Analysis (CVA), especially its visual aspects. It allows centroids of groups to be exhibited in increasing numbers of dimensions, together with information on within-group sample variation. Variables are represented by category-level-points (CLPs) which are a counterpart of numerically calibrated biplot axes for quantitative variables. Mechanisms are provided for relating the samples to their category levels, for giving convex regions to help predict categories, and for adding new samples. Inter-sample distance may be measured by any Euclidean embeddable distance. Computation is minimised by working in the K - 1 dimensional space containing the group centroids.The methodology is illustrated by an example with three groups and 37 samples but the number of samples size is not a serious limitation. The visualisation of group structure is the main focus of this paper; computational efficiency is a bonus.

A triplot for multiclass classification visualisation

Quadratic discriminant analysis is used when the assumption of equal covariance matrices for linear discrimination does not hold. The Canonical Variate Analysis biplot is used for graphical visualisation to accompany linear discriminant analysis. However, since class specific covariance matrix estimates are needed for quadratic discrimination the canonical transformation cannot be used. An alternative method of visually representing the discrimination and classification process is proposed: representing the sample points, classification regions based on quadratic discriminant analysis and including information on the variables. The methodology is further extended to other forms of multiclass classification and illustrated for support vector machines, classification trees, k -nearest neighbours and latent class analysis. In all these triplots three aspects are represented simultaneously, allowing for the representation of the relationships between samples and variables, relative to the classification regions.

Longitudinal characterization of nasopharyngeal colonization with Streptococcus pneumoniae in a South African birth cohort post 13-valent pneumococcal conjugate vaccine implementation

Monitoring changes in pneumococcal carriage is key to understanding vaccination-induced shifts in the ecology of carriage and impact on health. We longitudinally investigated pneumococcal carriage dynamics in infants. Pneumococcal isolates were obtained from nasopharyngeal (NP) swabs collected 2-weekly from 137 infants enrolled from birth through their first year of life. Pneumococci were serotyped by sequetyping, confirmed by Quellung. Pneumococci were isolated from 54% (1809/3331) of infants. Median time to first acquisition was 63 days. Serotype-specific acquisition rates ranged from 0.01 to 0.88 events/child-year and did not differ between PCV13 and non-PCV13 serotypes (0.11 events/child-year [95% CI 0.07–0.18] vs. 0.11 events/child-year [95% CI 0.06–0.18]). There was no difference in carriage duration between individual PCV13 and non-PCV13 serotypes (40.6 days [95% CI 31.9–49.4] vs. 38.6 days [95% CI 35.1–42.1]), however cumulatively the duration of carriage of non-PCV13 serotypes was greater than PCV13 serotypes (141.2 days (95% CI 126.6–155.8) vs. 30.7 days (95% CI 22.3–39.0). Frequently carried PCV13 serotypes included 19F, 9V, 19A and 6A, while non-PCV13 serotypes included 15B/15C, 21, 10A, 16F, 35B, 9N and 15A. Despite high immunization coverage in our setting, PCV13 serotypes remain in circulation in this cohort, comprising 22% of isolates. Individual PCV13 serotypes were acquired, on average, at equivalent rate to non-PCV13 serotypes, and carried for a similar duration, although the most common non-PCV13 serotypes were more frequently acquired than PCV13 serotypes.

Clinical educators' self-reported personal and professional development after completing a short course in undergraduate clinical supervision at Stellenbosch University

Background. In 2007, a Supervision Course in Undergraduate Clinical Supervision was developed at the Faculty of Medicine and Health Sciences at Stellenbosch University in South Africa. The target group was inter-professional clinical educators that are involved in student education on the clinical platform. Although the course participants were professionals and specialists in their own fields, the majority of clinical educators have very little or no knowledge of adult education. The Supervision Course aims to develop clinical supervision skills of clinical educators by exposing these supervisors to basic principles of education and specifically clinical teaching, resulting in quality education for undergraduate students. The aim of this study was to determine the impact of this short course on the personal and professional growth of the clinical educator. Methods. A qualitative study was performed, including an open-ended questionnaire that provided opportunity for the clinical educators to elaborate freely on their strengths, weaknesses and areas of desired improvement before and after the Supervision Course, and a semi-structured individual interview after the Supervision Course. The questionnaire data were categorised according to strengths, weaknesses and areas of desired improvement. An inductive approach was used to analyse the qualitative data. Key themes that emerged from the interviews were identified and grouped together in categories. Results. The results are summarised in table format to identify themes with supporting quotes. Conclusion. Although a small sample, this study demonstrates the personal and professional growth reported by attendees of a clinical supervision short course.

The pulp and paper properties of Sirex noctilio infested and fire-damaged thermomechanically pulped, South African grown Pinus patula.

Pinus patula is the softwood species most extensively planted in South Africa. However, large portions of these plantings are under threat from Sirex noctilio infestation and occasional forest fires. In this exploratory investigation, the effects of tree age, Sirex noctilio infestation and fire damage to wood from Pinus patula trees on their pulp and paper properties were evaluated. Pulp was produced using the thermomechanical pulping (TMP) process. The energy consumption required to pulp the different pulpwood materials was determined. Pulps were beaten for five different time periods to investigate the development of the fibre properties in response to increasing energy input. Paper properties such as burst, tear strength and breaking length were determined on handsheets manufactured from unbeaten and beaten pulps. Box and line plots and canonical variate analysis biplots were used to statistically analyse the data. It was found that the burst strength of paper produced from healthy trees was significantly higher than that from sirex-infested or fire damaged (burnt) trees. Similarly, the tear strength of paper from healthy and burnt trees was significantly better than from sirex-infested or young trees. No significant differences in breaking length were evident between the pulpwood materials and an increase in beating time did not lead to any improvements. From this study it can be concluded that wood from dead or dying, sirex-infested and young trees produced paper with consistently lower strength properties compared to wood obtained from healthy 12-year-old trees.