Introduction Ethnic differences in bone growth and proportions have previously been investigated in relation to bone fragility. Differential growth in the axial and appendicular skeletons has been suggested to predispose to differential susceptibility to fracture. The developmental origins of bone size and osteoporosis have also been investigated. However, the impact of foetal programming on body proportions and limb lengths in unknown. Objectives The aim of this study was to investigate the presence of ethnic and sex differences in axial and appendicular growth. Additionally, it was to investigate the impact of early life factors on skeletal dimensions and proportions in childhood . Methods Anthropometric measurements of stature, weight, sitting height and limb lengths were taken on 368 black and white, male and female 9 year old children. DXA scans of the distal ulna;distal radius; hip and lumbar spine were also obtained. The same measurements were obtained for 197 of the black children who had birthweight and weight and length data at 1 year. For the first part of the analyses, Analyses of Covariance were performed to assess differences in limb lengths adjusted for differences in stature. Multiple regression analyses were used to assess significant predictors of site-specific bone mass. Comparisons were made after adjustment for weight, weight and stature and weight and regional segment lengths. For the second part of the analyses, Analyses of Covariance were performed to assess differences in stature and regional segment lengths at different tertiles of birthweight, and weight and height at 1 year. Stepwise multiple regressions were performed with early life growth patterns to assess significant predictors of stature and regional segment lengths at 10 years. Results Black children had longer limbs but shorter trunks than white children. Regional segment length were a more significant predictor of site-specific bone mass than stature. In black boys birthweight had positive but weak associations with stature and regional segment length while in girls the association were marginal. In contrast, weight and height at 1yr had strong associations with stature and regional segment lengths. Conclusion There is a differential effect of ethnicity and sex on the growth of the axial and appendicular skeletons, and regional segment length is a better predictor of site-specific bone mass than stature. Early life growth has a long-term influence on stature, as well as on regional segment lengths but marginal effect on body proportions.

Globally, child mortality is a great concern, especially in resource-limited settings. The Millennium Development Goal (MDG) 4 was set with an aim to reduce under-5 child mortality by two-thirds between 1990 and 2015. This study examines mortality trends in infants, 1-4 and above 5-year-old children in rural KwaZulu-Natal, South Africa, the causes of death as well as the association of maternal HIV status and Antiretroviral Treatment (ART) usage to child mortality. We use a longitudinal birth cohort study design of children born between 1st January 2004 and 31st December 2010, in the Africa Centre Demographic Surveillance Area (DSA) in rural KwaZulu-Natal, South Africa. Children had to have been resident in the DSA at the time of birth. A total of 12,413 children born in the study period were eligible for this study. The main outcome measure was mortality either in infancy, the 1-4 year period or at 5 and above years of age, while assessing its association with maternal HIV and Antiretroviral Treatment uptake (ART) status on a time-varying basis. A total of 619 children died during the study period and mortality was observed to be highest in the infant group with 67% of the children dying in infancy. Fifteen percent of mothers were HIV positive at the time of birth of the child, about 59% were HIV negative while the HIV status of the rest was unknown. There was a three-fold increase in mortality observed for both infants and 1-4 year olds, who had mothers who were HIV infected compared to children whose mothers were HIV negative (p<0.05). Children whose mothers were on Antiretroviral Treatment (ART) however had a reduced mortality compared to those whose mothers were not on treatment. Infants and 1-4year olds whose mothers HIV status was not reported had a two-fold increase in mortality. Low maternal education, single motherhood, multiple births and parity of four or more children were also associated with increased child mortality. We concluded that although mortality varied by the age of the child, children born to mothers who were HIV positive had higher mortality rates than children born to HIV negative mothers but being on Anti Retroviral Treatment (ART) reduced children mortality. Interventions targeting HIV positive pregnant women and mothers should be carried out in the study area, with specific emphasis on reducing child mortality associated with maternal HIV status.

Thesis (Ph.D.)--University of the Witwatersrand, Faculty of Health Sciences, 2012 / Osteoporosis has been described as a paediatric disease with geriatric consequences. This thesis explored the associations between proximal, historical and predictive genetic and environmental factors affecting bone mass and bone size in socio-economically- and environmentally-disadvantaged black and -advantaged white pre- and early-pubertal South African children. Data were collected from 476 children (182 black boys, 72 white boys, 158 black girls, 64 white girls) of mean age 10.6 years (range: 10.0-10.9), 406 biological mothers and 100 biological fathers. The main findings were that black children and their parents compared to white, had greater DXA-measured BMC at the femoral neck regardless of the way in which BMC was corrected for size (height, weight, BA and/or BAPC) and greater bone strength. Lumbar spine BMC was greater or similar depending on which measures were used to correct BMC for size. At the whole body, mid radius and distal one third of the radius, BMC varied between children, and between their parents, and were dependent on which measures were used to correct BMC for size. Weight at 1 year (WT1), length at 1 year (LT1) and birth weight (BW), were significant predictors of BMC of the femoral neck (P<0.05-0.01) after correcting BA and BMC for race/ethnicity, gender, age, socioeconomic status, bone age, height and weight at 10 years. Maternal and paternal heritability was estimated to each be ~30% in both black and white subjects. The main conclusion was that ethnicity is the single most important proximal factor affecting bone mass and bone size in 10 year old South African children. Black children demonstrate a superior bone mass and bone strength at the femoral neck. Historical and predictive factors however indicate that black children have not been programmed for optimal bone health in utero and early life, nor are contemporary environmental factors favourable for the maximisation of peak bone mass. This cohort may be at risk of developing osteoporosis as an elderly population, particularly at the lumbar spine and forearm.

Aims: 1) To determine the incidence or rates of fractures, the common sites of fractures, the causes of fractures and grades of trauma causing fractures in urban South African children of different ethnic groups from birth until 17/18 years of age. 2) To investigate the association between fracture prevalence, bone mass and physical activity in South African children. 3) To assess associations of fracture prevalence and bone mass in adolescents with maternal fracture history and bone mass and sibling fracture history. Design: Using the Birth to Twenty longitudinal cohort of children, we obtained retrospective information on fractures and their sites from birth to 14.9 years of age on 2031 participants. The ethnic breakdown of the children was black (B) 78%, white (W) 9%, mixed ancestry (MA) 10.5% and Indian (I) 1.5%. Using the Bone Health cohort of the Birth to Twenty longitudinal study, we retrospectively obtained information of lifetime fractures until age 14.9 years in 533 subjects. Bone mass (measured by DXA), anthropometric data, physical activity scores and skeletal maturity were obtained at age 10 and 15 years. Comparisons were made between those who did and did not fracture within the same sex and ethnic groups. The third component of the thesis utilized data from 1389 adolescent-biological mother pairs of the Birth to Twenty (Bt20) longitudinal study. Questionnaires were completed on adolescent fractures until 17/18 years of age and on sibling fractures. Biological mothers completed questionnaires on their own fractures prior to the age of 18 years. Anthropometric and bone mass data on adolescent-biological mother pairs were collected. Results: Twenty two percent of children had sustained a fracture one or more times during the first 15 years of life (males 27.5% and females 16.3%; p<0.001). The percentage of children fracturing differed between the ethnic groups (W 41.5%, B 19%, MA 21%, I 30%; p<0.001). Of the children reporting fractures, 20% sustained multiple fractures. The most common site of fracture was the upper limb (57%). In the second component of the thesis, white males who fractured were found to be significantly taller (10 years p < 0.05), more physically active (15 years p < 0.01) and had higher lean body mass (10 years p=0.001; 15 years p<0.05) than those who did not fracture; while white females, who fractured, were fatter (10 and 15 years p< 0.05), than their nonfracturing peers. White males who fractured had greater BA (bone area) and BMC (bone mineral content) at most sites at 10 and 15 years; BA and BMC were no different between fracturing and non-fracturing children in the other ethnic groups. No anthropometric or bone mass differences were found between black children with or without fractures. The third component of the thesis showed that an adolescent’s risk of lifetime fracture decreased with increasing maternal lumbar spine (LS) BMC (24% reduction in fracture risk for every unit increase in maternal LS BMC Z-score) and increased if they were white, male or had a sibling with a history of fracture. Adolescent height, weight, male gender, maternal BA and BMC, and white ethnicity were positive predictors of adolescent bone mass. White adolescents and their mothers had a higher fracture prevalence (adolescents: 42%, mothers: 31%) compared to the black (adolescents: 20%, mothers: 6%) and mixed ancestry (adolescents: 20%, mothers: 16%) groups. Conclusion: More than twice as many South African white children fracture compared to black and mixed ancestry children. This is the first study to show ethnic differences in fracture rates among children; a pattern that is similar to that found in South African postmenopausal women. The factor associated with fractures in white boys appears to be participation in sports activities, while in white girls obesity appears to play a role. We were unable to find any factors that could explain fractures in black children. Unlike the findings of some other studies, fractures in these children were not associated with lower bone mass or reduced skeletal size. Maternal bone mass also appears to play a role in determining fracture incidence in children, as the mother’s bone mass has a significant inverse association with their off-springs’ fracture risk throughout childhood and adolescence. Furthermore, there is a strong familial component in fracture risk among South African adolescents and their siblings, as evidenced by the increased risk of fracture in siblings of index children who have fractured during childhood and adolescence. Differences in fracture rates and bone mass between families and individuals of different ethnic origins may be due to differing lifestyles and/or genetic backgrounds.

A Thesis Submitted to the Faculty of Health Sciences, University of the Witwatersrand in partial fulfilment of the requirements for the Degree of Master of Science in Epidemiology Major Area-Subject: Biostatistics and Epidemiology November 2014 / Background: Malaria is a serious public health challenge in sub-Saharan Africa with children under five being the most vulnerable, and a child dies every 30 seconds from it. Therefore, it is important to investigate malaria’s direct and indirect determinants in specific sub-Saharan populations as well as identifying malaria hotspots in order to have informed and targeted preventative interventions. Rationale: Given the extent and seriousness of malaria in Southern Africa, understanding fully the factors associated with malaria is important in successfully fighting it. Therefore, understanding the determinants of malaria in children under five is important in working towards eliminating malaria in sub-Saharan populations. Objectives: This study’s objectives were:  To describe demographic, behavioral and environmental determinants (factors) associated with malaria episodes in under fives in households in Malawi in the year 2012  To investigate the determinants of malaria episodes in children under five years in Malawi in 2012  To compare spatial distribution of malaria episodes in households in Malawi in 2012. Methods: This study was a secondary data analysis based on data from the Malawi 2012 Malaria Indicator Survey (MIS) obtained from Demographic and Health Survey (DHS) program website. The outcome variable was positive blood smear result for malaria in children less than five years, after an initial positive rapid malaria diagnostic test done at the homestead. We controlled for confounders after propensity score matching in order to reduce selection bias. Cases and controls were matched based on their propensity scores. Statistical modelling was done using logistic regression as well as generalized structural equation modeling (G-SEM) to model direct and indirect effects on the outcome. Poisson regression was done to determine associations between the outcome (positive blood smear malaria result) and selected explanatory variables at household level and we then introduced a structured and unstructured random effect to measure spatial effects if any of malaria morbidity in children under the age of five. Results: The matched data had 1 325 children with 367 (24.3%) having blood smear positive malaria. Female children made up approximately 53% of the total study participants. Child related variables (age, haemoglobin and position in household) as well as wealth index were significant (directly and indirectly) with p values <0.001. Socio-economic status (SES) [Odds ratio (OR) = 0.96, 95% Confidence interval (CI) = 0.92, 0.99] and primary level of education [OR = 0.50, 95%CI = 0.32, 0.77] were important determinants. The spatially structured effects accounted for more than 90% of random effects as these had a mean of 1.32 (95% Credible Interval (CI) =0.37, 2.50) whilst spatially unstructured had a mean of 0.10(CI=9.0x10-4, 0.38). The spatially adjusted significant variables on malaria morbidity were; type of place of residence (Urban or Rural) [posterior odds ratio (POR) =2.06; CI = 1.27, 3.34], not owning land [RR=1.77; CI= 1.19, 2.64], not staying in a slum [RR=0.52; CI= 0.33, 0.83] and enhanced vegetation index [RR=0.02; CI= 0.00, 1.08]. A trend was observed on usage of insecticide treated mosquito nets [POR=0.80; CI= 0.63, 1.03]. Conclusion: Socio-economic status (directly and indirectly) and education are important factors that influence malaria control. The study showed malaria as a disease of poverty with significant results in slum, type of place of residence as well as ownership of land. It is important that these factors be taken into consideration when planning malaria control programs in order to have effective programs. Direct and indirect effect modelling can also provide an alternative modelling technique that incorporates indirect effects that might not be of significance when modeled directly. This will help in improving malaria control. Enhanced vegetation index was also an important factor in malaria morbidity but precipitation and temperature suitability index were not significant factors.

'n SKRIPSIE VOORGELe AAN DIE MEDTESE FAKULTEIT, UNIVERSITEIT VAN DIE W1TWATERSRAND, JOHANNESBURG TER GEDEELTEL1KE VOLDOENING AAN DIE HAMSTER SCIENTIFICAE IN ARREIDSTERAPIE JOHANNESRURi 1989 / Arbeldsterapeute ontvsng dikwels verwysings van kinders met leerprobleme omdat 'n nnderliggende oorsaak moontHk v ls u e e lperseptueel van aard kan wees. Daar is v ie r visueel-perseptuele toetse wat gereeld gebruik word om visueel-perseptuele probieme vas t e s t e l , met min kennis oor w atter een van die v ie r toetse probieme die beste aandui en of d ie toetse wel k o rrele er net akademiese probieme of mislukkinq op skool. Die essensie van die saak word verder beklemtoon deur die totstandkoming van verskeie remediMrende skole in S u id -A frika waar perseptuele vermo^ns en die evaluering en remediBring daarvan, 'n belangrike fa s e t vorm. C it noodsaak navorsing om die rol wat visu eel-p ersep tu ele vermoBns by kinders met leerprobleme speel, u i t t e l i g . Die doel van die s tu d ie , naamlik om te bepaal of daar en" > verband tussen die onderskeie v ie r visueel-perseptuele to*, r. bestaan en hul k o rre la s ie met akademiese probieme soos ervaar deur leergestremde kin ders, word dus deur die kandidaat as u ite rs belangrik beskou, aangesien Arbeidsterapeute al hoe neer betrek word in die evaluasie en remediBrinq van leergestremde kinders.

Research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the Master of Science in Occupational Therapy, Johannesburg, June 2013 / The effectiveness of the Stetro pencil grip in 45 Grade 2 learners with handwriting difficulties was investigated. Monthly assessments considered descriptors including the position joints when writing, the position of the pencil in the hand, hand and arm movements, arm position and posture when writing as well as pencil grasp, the speed and quality of handwriting and tripod pinch strength. The experimental participants used a Stetro pencil grip for two months after which it was removed for one month. The control participants wrote without a pencil grip. Statistically significant improvement was found for the experimental group in the efficiency of their pencil grasps and their use of their fingers when writing. The quality and speed of writing and the pinch strength improved in both groups with the experimental group showing significant change in their index finger DIP position. The use of the Stetro pencil grip was effective in resolving inefficient pencil grasps in 70% of the experimental group.

Background: Lower respiratory tract infections (LRTI) are a leading cause of morbidity and mortality in young children. A number of new viruses associated with LRTI in young children have recently been discovered. These include Human Bocavirus (HBoV), Human Polyomavirus strains WU (WUPyV) and KI (KIPyV) and Human Coronavirus strains NL63 (HCoV-NL63) and HKU-1 (HCoV-HKU-1). There is, however, limited data on the epidemiology of these newly discovered respiratory viruses in industrializing country settings, including South Africa. Objective: To determine the clinical epidemiology of HBoV, HCoV-NL63, HCoVHKU1, HCoV-OC43, HCoV strain 229E (HCoV- 229E), WUPyV, KIPyV and human rhinovirus (HRV) in young children. Methods: Nasopharyngeal aspirates where taken from children who were hospitalized at Chris Hani Baragwanath Hospital between February 2000 and January 2002 with severe LRTI. These children had been enrolled in a double-blind, randomized, placebo-controlled trial of a 9-valent pneumococcal conjugate vaccine (PCV). Nucleic acid extraction was undertaken from archived nasopharyngeal aspirate samples and the respiratory viruses identified using real time duplex PCR. The study was limited to examining samples from HIV uninfected children with LRTI who were less than 24 months of age. Results: Overall, samples were available for 895 of 1565 nasopharyngeal aspirates, from children hospitalized with LRTI, collected from February 2000 to January 2002. A comparison between those LRTI episodes for which samples were unavailable compared to those for which samples were available indicated that children in whom samples were unavailable were younger than children with available samples (9.9±6.4 vs. 11.8±6.5 months; p<0.0001). In addition there was a higher frequency of wheezing episodes in children for whom samples were unavailable (60.4 vs. 54.6%; p=0.022). The overall prevalence of the viruses in children with any LRTI were 33.2% for HRV, 21.2% for HBoV, 16.1% for WUPyV, 10.1% for HCoV-OC43, 7.0% for KIPyV, 3.2% for HCoVNL63, 2.6% for HCoV-HKU-1, and 0.6% for HCoV-229E. There was a higher probability of detecting a selected virus in LRTI episodes among PCV-compared to placebo-recipients for HBoV (24.2% vs. 18.2%, respectively; p=0.028) and HRV (36.7% vs. 29.5%, respectively; p=0.023). Conversely, viruses identified more frequently in LRTI episodes among children who received placebo compared to PCV-recipients included WUPyV (20.2% vs. 12.1%, respectively; p=0.001), KIPyV (10% vs. 4.2%, respectively; p=0.001), HCoV-OC43 (14.1% vs. 6.2%, respectively; p≤0.0001) and HCoV-HKU1 (4.5% vs. 0.1%, respectively; p≤0.0001). Overall, the prevalence of the studied-viruses in the subgroup of children categorized as having bronchiolitis was 33.8% for HRV, 33.4% for WUPyV, 22.3% for HBoV, 11.1% for HCoVOC43, 5.3% for KIPyV, 2.3% for HCoV-NL63, 1.9% for HCoV-HKU1 and 0.4% for HCoV-229E. Viruses more commonly identified in placebocompared to PCV-recipients among children hospitalized with bronchiolitis included WUPyV (20.0% vs. 12.3%, respectively; p=0.029), HCoV-OC43 (15.9% vs. 7.2%, respectively; p=0.004) and HCoV-HKU1 (3.6% vs. 0.5%, respectively; p=0.015). The prevalence of the newly studied viruses in the subgroup of children categorized as having clinical pneumonia was 30.8% for HRV, 20.3% for HBoV, 16.4% for WUPyV, 9.1% for HCoVOC43, 8.6% for KIPyV, 4.1% for HCoV-NL63, 3.2% for HCoV-HKU1 and 0.6% for HCoV-229E. Viruses identified more frequently among placebo- compared to PCV-recipients, in those with clinical pneumonia, included WUPyV (20.4% vs. 11.9%, respectively; p=0.013),HCoV-HKU1 (5.3% vs. 0.9%, respectively; p=0.008). Conversely, HCoV-OC43 was identified more frequently in children with clinical pneumonia among PCV- (5.0%) compared to placebo-recipients (2.7%, p=0.004). There were seasonal peaks, during autumnwinter months (April to June), in the detection of HRV, WUPyV, HCoV-OC43, HCov-NL63 and HCoV-HKU1, whereas KIPyV, HBoV and HCoV- 229E were identified perennially. Conclusion: Prevalence of respiratory viruses is high in industrializing countries and the presence of these viruses is frequently associated with co-infections of more than one etiological agent. In industrializing countries such as in South Africa, the recently identified respiratory viruses play a role in development of pneumonia. KIPyV (12.7% vs. 4.1%, respectively; p=0.001),

A research report submitted to the Faculty of the Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree of Master of Medicine in the branch of Nuclear Medicine. Johannesburg 2011 / Paediatric Nuclear Medicine is associated with a high preponderance of nephro-urological investigations. This preponderance has been attributed to the relatively higher occurrence of urinary tract infections and their sequelae in children, as well as to improved antenatal detection of anomalies of the genitor-urinary tract. Nuclear Medicine is involved in the management of these children to assist with diagnosis, clinical decision-making and follow-up of global and relative renal function. As such, these scans need to be carried out as efficiently as possible. International protocols established by the European and American societies of Nuclear Medicine have been formulated to aid the Nuclear Medicine technologist and physician in performing these procedures and interpreting them correctly. Audits of Nuclear Medicine practice are performed in order to assess compliance with these guidelines. A clinical audit has been defined as “a systematic and critical analysis of the quality of medical care, including procedures for diagnosis and treatment.” An audit of the renal paediatric procedures carried out in the Division of Nuclear Medicine at the Charlotte Maxeke Johannesburg Academic Hospital was performed retrospectively on studies carried out from January 2006 - December 2009, as well as a prospective study of procedures from February – July 2010. Results showed overall conformity to most of the recommended practices of the EANM guidelines. As occurs in most institutions, each institution may adapt guidelines to comply with local circumstances.

Three-dimensional (3D) object perception is critical for comprehending and interacting with the world. It develops during infancy and continues through adulthood. One powerful cue used for object perception is uniform coherent motion. The present paper first briefly reviews the current literature concerning object perception using random-dot stimuli and structure-from-motion (SFM) displays. To extend our knowledge in this area, two new studies were conducted to further our understanding of how infants process 3D shape in SFM stimuli. Study 1 examined infants of two age groups (3-5 month-olds and 8-9 month-olds) in a familiarization phase and a test phase. In the familiarization phase, infants were exposed to one of two SFM shapes (cube or cylinder) and in the test phase infants viewed both SFM shapes side-by-side. Extraction of shape was measured through novelty preferences. Results of Study 1 suggest that both age groups successfully extracted 3D shape. Study 2 served as a replication and extension, with the added control for the variable rotational axis. When this variable was controlled for, 3-5 month-olds failed to show a novelty preference during the test phase. These results suggest not only that infants were attending to both the global shape presented in the SFM stimuli as well as the detailed component of the rotational axis of the stimuli, but also that adding the extra change in the component of rotational axis to SFM stimuli makes the task of extracting shape more difficult for infants. These findings contribute to the infant literature by furthering the understanding of infant shape perception.