Maximizing Access and Minimizing Barriers to Research in Low- and Middle-Income Countries: Open Access and Health Equity.

Access to published research has always been difficult for researchers and clinicians in low- and middle-income countries, because of the cost of and lack of access to the relevant publications. The dramatic recent increase in electronic research publications has resulted in a marked improvement in reader access to these publications through their mainly Open Access policies, however the costs of processing of submissions and publication have now become the burden of the researchers wishing to publish, rather than the readers. For many researchers working in LMIC, the Article Processing Charges (APC) are prohibitive, hampering the publication of research being conducted in and relevant to these countries. A number of grant funding agencies and international not-for-profit organizations are trying to address these issues by including funding for article publications in their grants, or by supporting publishing entities by subsiding the cost of publication, but more needs to be done by major journal publishers through markedly reducing the APC being charged to researchers in LMIC for open access facilities.

Prevalence and predictors of vitamin D deficiency in young African children.

BACKGROUND: Children living in sub-Saharan Africa have a high burden of rickets and infectious diseases, conditions that are linked to vitamin D deficiency. However, data on the vitamin D status of young African children and its environmental and genetic predictors are limited. We aimed to examine the prevalence and predictors of vitamin D deficiency in young African children. METHODS: We measured 25-hydroxyvitamin D (25(OH)D) and typed the single nucleotide polymorphisms, rs4588 and rs7041, in the GC gene encoding the vitamin D binding protein (DBP) in 4509 children aged 0-8 years living in Kenya, Uganda, Burkina Faso, The Gambia and South Africa. We evaluated associations between vitamin D status and country, age, sex, season, anthropometric indices, inflammation, malaria and DBP haplotypes in regression analyses. RESULTS: Median age was 23.9 months (interquartile range [IQR] 12.3, 35.9). Prevalence of vitamin D deficiency using 25(OH)D cut-offs of < 30 nmol/L and < 50 nmol/L was 0.6% (95% CI 0.4, 0.9) and 7.8% (95% CI 7.0, 8.5), respectively. Overall median 25(OH)D level was 77.6 nmol/L (IQR 63.6, 94.2). 25(OH)D levels were lower in South Africa, in older children, during winter or the long rains, and in those with afebrile malaria, and higher in children with inflammation. 25(OH)D levels did not vary by stunting, wasting or underweight in adjusted regression models. The distribution of Gc variants was Gc1f 83.3%, Gc1s 8.5% and Gc2 8.2% overall and varied by country. Individuals carrying the Gc2 variant had lower median 25(OH)D levels (72.4 nmol/L (IQR 59.4, 86.5) than those carrying the Gc1f (77.3 nmol/L (IQR 63.5, 92.8)) or Gc1s (78.9 nmol/L (IQR 63.8, 95.5)) variants. CONCLUSIONS: Approximately 0.6% and 7.8% of young African children were vitamin D deficient as defined by 25(OH)D levels < 30 nmol/L and < 50 nmol/L, respectively. Latitude, age, season, and prevalence of inflammation and malaria should be considered in strategies to assess and manage vitamin D deficiency in young children living in Africa.

Adolescent growth and BMI and their associations with early childhood growth in an urban South African cohort.

OBJECTIVES: The timing and magnitude of adolescent growth may be influenced by ethnicity and early life factors. We aimed to (a) characterize ethnic differences in the magnitude, timing, and intensity of adolescent growth in height, weight, and BMI; (b) assess the effect of early childhood growth on adolescent growth in black children. METHODS: Data were from the Birth to Twenty Plus cohort (Bt20+) in Johannesburg, South Africa (n = 3273). Height, weight, and BMI were modeled with ethnic comparisons using the SuperImposition by Translation and Rotation for 2089 participants who had data from 7 to 23 years. Relative weight gain and relative linear growth between 0 and 24 months and 24 and 60 months were generated. Multiple regression analyses were used to assess associations between childhood and adolescent growth. RESULTS: White children were 5 cm (SE: 0.7) taller than black children through adolescence. Black boys had a later timing of adolescent height (0.65 years ±0.12) than white boys, which in black girls was 0.24 years (0.11) earlier than in white girls. Black girls had faster BMI velocity than white girls. Among black children, birth weight and both relative weight gain 0 to 24 and relative linear growth between 3 and 24 months and 24 and 60 months were positively associated with the magnitude of adolescent growth and negatively associated with timing. CONCLUSION: Sex dimorphism in ethnic differences in timing of adolescent height growth may reflect some yet unexplained drivers for rapid weight gain and obesity in black females but not black males. Rapid weight gain in early life may contribute to faster adiposity accrual in adolescence.

Renal dysfunction, rod-cone dystrophy, and sensorineural hearing loss caused by a mutation in RRM2B.

More than two decades ago, a recessive syndromic phenotype affecting kidneys, eyes, and ears, was first described in the endogamous Afrikaner population of South Africa. Using whole-exome sequencing of DNA from two affected siblings (and their carrier parents), we identified the novel RRM2B c.786G>T variant as a plausible disease-causing mutation. The RRM2B gene is involved in mitochondrial integrity, and the observed change was not previously reported in any genomic database. The subsequent screening revealed the variant in two newly presenting unrelated patients, as well as two patients in our registry with rod-cone dystrophy, hearing loss, and Fanconi-type renal disease. All patients with the c.786G>T variant share an identical 1.5 Mb haplotype around this gene, suggesting a founder effect in the Afrikaner population. We present ultrastructural evidence of mitochondrial impairment in one patient, to support our thesis that this RRM2B variant is associated with the renal, ophthalmological, and auditory phenotype.

The prevalence of malnutrition and growth percentiles for urban South African children.

BACKGROUND: Low- and middle-income countries (LMIC) are experiencing a double-burden of malnutrition characterised by high prevalence of both under- and over-nutrition. We set out using data from the mixed-longitudinal Birth-to-Twenty Plus (Bt20+) birth cohort, to evaluate the patterns of malnutrition and growth in a large South African (SA) city by; (i) assessing the prevalence of undernutrition from birth to 5 years of age and overweight and obesity from ages 2 to 21 years in black and white, male and female children, and (ii) determining percentiles for height, weight, BMI, waist and hip circumferences and comparing the centiles to American and Dutch references. METHODS: Height, weight, waist and hip circumferences were measured on urban black and white SA children from the Bt20+. A total of 3273 children born between April and June 1990 in the Greater Johannesburg Metropolitan area were included in the cohort. Z-scores were derived using the WHO 2006 child growth standards (0-5 years), for defining stunting, underweight and wasting. The International Obesity Task Force (IOTF) references were used to define overweight and obesity. Percentiles were developed using the lambda mu sigma (LMS) method and compared to American and Dutch references. RESULTS: Black children were consistently shorter and black males lighter than white children and American references. The prevalence of stunting peaked at 2 years and was significantly higher in males than females and in black than white children. Black females had a greater prevalence of overweight and obesity than black males from 10 to 17 years. The percentiles for black females for weight and BMI were similar to those of South African white and American references but both black and white South African females had lower waist circumferences than American references. CONCLUSION: The growth percentiles show that young South African urban black females are experiencing general but not central obesity due to a secular change which is faster in weight than height. High levels of undernutrition persist alongside high levels of over-nutrition with adolescence being a critical period for the upsurge in obesity in females. Early intervention is needed to combat the rise in obesity.

Sanitation and diarrhoea in infancy and CRP level at 18 years: the birth-to-twenty plus cohort.

Background: Cardiometabolic disease is associated with chronic low-grade inflammation. While low birthweight, childhood stunting and rapid weight gain predict higher adult high-sensitivity C-reactive protein (hs-CRP) concentrations, associations between childhood infections and adulthood CRP are inconsistent.Aim: To assess the associations between sanitation, diarrhoea and a combined score of both from birth to age 2 years and hs-CRP at age 18 years, independently of early life nutrition and adult adiposity.Subjects and methods: This study collected data on sanitation and diarrhoea episodes from birth to 2 years on 756 participants of the Birth-to-Twenty Plus cohort, a birth cohort initiated in South Africa in 1990, and calculated a combined score of both variables. Anthropometry was measured at 2 years and 18 years and hs-CRP at 18 years.Results: Of the participants, 29.5% had no access to indoor flush sanitation and 38.2% experienced ≥1 diarrhoea episode between birth and 2 years. Not having access to indoor flush sanitation and experiencing ≥1 diarrhoea episodes were associated with 1.50 mg/L and 1.52 mg/L higher hs-CRP, respectively. Prevalence of both burdens in infancy was associated with a 2.18 mg/L higher hs-CRP.Conclusion: In this population, poor sanitation and diarrhoea in early life predict elevated CRP in young adulthood, independently of early life nutrition and adiposity.

Life History theory hypotheses on child growth: Potential implications for short and long-term child growth, development and health.

Life history theory integrates ecological, physiological, and molecular layers within an evolutionary framework to understand organisms' strategies to optimize survival and reproduction. Two life history hypotheses and their implications for child growth, development, and health (illustrated in the South African context) are reviewed here. One hypothesis suggests that there is an energy trade-off between linear growth and brain growth. Undernutrition in infancy and childhood may trigger adaptive physiological mechanisms prioritizing the brain at the expense of body growth. Another hypothesis is that the period from conception to infancy is a critical window of developmental plasticity of linear growth, the duration of which may vary between and within populations. The transition from infancy to childhood may mark the end of a critical window of opportunity for improving child growth. Both hypotheses emphasize the developmental plasticity of linear growth and the potential determinants of growth variability (including the role of parent-offspring conflict in maternal resources allocation). Implications of these hypotheses in populations with high burdens of undernutrition and infections are discussed. In South Africa, HIV/AIDS during pregnancy (associated with adverse birth outcomes, short duration of breastfeeding, and social consequences) may lead to a shortened window of developmental plasticity of growth. Furthermore, undernutrition and infectious diseases in children living in South Africa, a country undergoing a rapid nutrition transition, may have adverse consequences on individuals' cognitive abilities and risks of cardio-metabolic diseases. Studies are needed to identify physiological mechanisms underlying energy allocation between biological functions and their potential impacts on health.

Comparison of Limestone and Ground Fish for Treatment of Nutritional Rickets in Children in Nigeria.

OBJECTIVE: To determine whether children with calcium-deficiency rickets respond better to treatment with calcium as limestone or as ground fish. STUDY DESIGN: Nigerian children with active rickets (n = 96) were randomized to receive calcium as powdered limestone (920 mg of elemental calcium) or ground fish (952 mg of elemental calcium) daily for 24 weeks. Radiographic healing was defined as achieving a score of 1.5 or less on a 10-point scale. RESULTS: The median (range) age of enrolled children was 35 (6-151) months. Of the 88 children who completed the study, 29 (66%) in the ground fish group and 24 (55%) in the limestone group achieved the primary outcome of a radiographic score of 1.5 or less within 6 months (P = .39). The mean radiographic score improved from 6.2 ± 2.4 to 1.8 ± 2.2 in the ground fish group and from 6.3 ± 2.2 to 2.1 ± 2.4 in the limestone group (P = .68 for group comparison). In an intention to treat analysis adjusted for baseline radiographic score, age, milk calcium intake, and serum 25-hydroxyvitamin D concentration, the response to treatment did not differ between the 2 groups (P = .39). Younger age was associated with more complete radiographic healing in the adjusted model (aOR 0.74 [95% CI 0.57-0.92]). After 24 weeks of treatment, serum alkaline phosphatase had decreased, calcium and 25-hydroxyvitamin D increased, and bone mineral density increased in both groups, without significant differences between treatment groups. CONCLUSION: In children with calcium-deficiency rickets, treatment with calcium as either ground fish or limestone for 6 months healed rickets in the majority of children.

Has the prevalence of stunting in South African children changed in 40 years? A systematic review.

BACKGROUND: In the last 20 years, South Africa has experienced political, economic, and demographic transitions accompanied by an epidemiological transition. Like several sub-Saharan countries, the South African population is facing both under-and over-nutrition, and nutrition and lifestyle related chronic disease while the burden of infectious disease remains high. It is critical to understand these trends overtime in order to highlights the pitfalls and successful measures initiatives taken in the efforts to tackle malnutrition. The objective of this systematic review is to investigate the changes in the prevalence of stunting, a chronic form of undernutrition, in South Africa over 40 years, and to derive lessons from the South African experience, a country in an advanced process of transition in sub-Saharan Africa. METHODS: We undertook a systematic review of publications selected from PubMed, Science Direct and Scopus. We included studies and surveys published between 1970 and 2013 if they reported the prevalence of stunting (low height-for-age) in children under-6 years of age living in South Africa. We excluded studies conducted in health facility outpatients or hospital wards, or children with known chronic and acute infectious diseases. We extracted Date of data collection, study setting, ethnicity, age, sex, sample size, growth references/standards, diagnostic criteria for stunting and prevalence of stunting from each study. RESULTS: Over the last decade, the national prevalence of stunting has decreased. However, between and within provincial, age and ethnic group disparities remain. Unlike other countries in sub-Saharan Africa, no sex or rural/urban differences were found in preschool children. However, the analysis of long-term trends and identification of vulnerable groups is complicated by the use of different growth references/standards and sampling methods. CONCLUSION: Despite economic growth, political and social transitions, and national nutritional programs, stunting remains stubbornly persistent and prevalent in South Africa. A multi-sectoral and public health approach is needed to: (i) better monitor stunting over time, (ii) combat malnutrition during the first thousand days of life through continued efforts to improve maternal nutrition during pregnancy and infant feeding practices.

Blood pressure tracking in urban black South African children: birth to twenty cohort.

BACKGROUND: Hypertension is an emerging public health problem in South Africa. Recent evidence from longitudinal studies has shown that hypertension in adulthood can be traced back to childhood. There is scarcity of longitudinal data on paediatric blood pressure (BP) particularly in African populations. The objective of this study is to assess the prevalence of hypertension and evaluate BP tracking between childhood and late adolescence among South African black Children. METHODS: This study utilized data from the Birth to Twenty cohort, which is comprised of children born in Soweto, Johannesburg in 1990 (N = 3273, 78.5% black). Data on BP and anthropometry were collected at six follow-up periods between ages 5 and 18 years. Blood pressure status was classified using the Fourth report on National High Blood pressure program in children and adolescents. Pearson correlation coefficients and relative risk ratios (RR) were used to describe tracking of BP between childhood and late adolescence. RESULTS: The overall point prevalence ranged from 9.2 to 16.4% for prehypertension and 8.4 to 24.4% for hypertension. Tracking coefficients ranged from 0.20 to 0.57 for SBP and 0.17- 0.51 for DBP in both sexes over the 14 years of measurement. The proportion of children who maintained an elevated BP status between childhood, adolescence and age 18 years ranged from 36.1% at age 5 years to 56.3% at age 13 years. Risk of having elevated BP at 18 years ranged from; RR: 1.60 (95 % CI: 1.29-2.00) at 5 years to RR: 2.71 (95 % CI: 2.32-3.17) at 14 years of age. CONCLUSIONS: This study reports high prevalence of elevated BP which tracks from early childhood into late adolescence. These findings emphasize the importance of early identification of children at risk of developing elevated BP and related risk factors plus timely intervention to prevent hypertension in adulthood.

Corpus callosum thickness on mid-sagittal MRI as a marker of brain volume: a pilot study in children with HIV-related brain disease and controls.

BACKGROUND: Corpus callosum thickness measurement on mid-sagittal MRI may be a surrogate marker of brain volume. This is important for evaluation of diseases causing brain volume gain or loss, such as HIV-related brain disease and HIV encephalopathy. OBJECTIVE: To determine if thickness of the corpus callosum on mid-sagittal MRI is a surrogate marker of brain volume in children with HIV-related brain disease and in controls without HIV. MATERIALS AND METHODS: A retrospective MRI analysis in children (<5 years old) with HIV-related brain disease and controls used a custom-developed semi-automated tool, which divided the midline corpus callosum and measured its thickness in multiple locations. Brain volume was determined using volumetric analysis. Overall corpus callosum thickness and thickness of segments of the corpus callosum were correlated with overall and segmented (grey and white matter) brain volume. RESULTS: Forty-four children (33 HIV-infected patients and 11 controls) were included. Significant correlations included overall corpus callosum (mean) and total brain volume (P = 0.05); prefrontal corpus callosum maximum with white matter volume (P = 0.02); premotor corpus callosum mean with total brain volume (P = 0.04) and white matter volume (P = 0.02), premotor corpus callosum maximum with white matter volume (P = 0.02) and sensory corpus callosum mean with total brain volume (P = 0.02). CONCLUSION: Corpus callosum thickness correlates with brain volume both in HIV-infected patients and controls.

Effect of adiposity, season, diet and calcium or vitamin D supplementation on the vitamin D status of healthy urban African and Asian-Indian adults.

Vitamin D deficiency has been implicated in the aetiology of infectious diseases and metabolic syndrome. These diseases are prevalent in the African and Asian-Indian populations of South Africa; however, there is limited data on 25-hydroxyvitamin D (25(OH)D) concentrations in these populations. The aim of the present study was to assess the vitamin D status and its predictors in healthy adults in Johannesburg. We assessed the vitamin D status of 730 adult African and Asian-Indian subjects residing in Johannesburg. The contributions of sun exposure, season, dietary intake of Ca and vitamin D, total body fat and body fat distribution to 25(OH)D concentrations were assessed. The concentrations of 25(OH)D were measured by HPLC. The contribution of 25(OH)D3 to total 25(OH)D concentrations was assessed. The mean age of the subjects was 42·6 (SD 13·1) years (range: 18-65). Concentrations of 25(OH)D < 30 nmol/l were found in 28·6 % of the Asian-Indian subjects in comparison with 5·1 % of the African subjects (P< 0·0001). Parathyroid hormone (PTH) concentrations were negatively associated with 25(OH)D concentrations, while season and sun exposure were positive predictors explaining 16 % of the variance in 25(OH)D concentrations (P< 0·0001) in the African subjects. In the Asian-Indian subjects, PTH concentrations were negatively associated with 25(OH)D concentrations, while male sex, season and Ca supplementation were positive predictors and explained 17 % of the variance in 25(OH)D concentrations (P< 0·0001). In the multivariate regression analysis, neither total body fat nor body fat distribution was predictive of 25(OH)D concentrations in either group. In conclusion, factors such as sun exposure, dietary supplement use and ethnicity are important determinants of plasma 25(OH)D concentrations.

Dietary intake and body composition in HIV-positive and -negative South African women.

OBJECTIVE: The present paper examines dietary intake and body composition in antiretroviral (ARV)-naïve HIV-positive compared with HIV-negative South African women, as well as the impact of disease severity on these variables. DESIGN: Baseline data from a longitudinal study assessing bone health in HIV-negative and HIV-positive premenopausal South African women over 18 years of age were used. Anthropometry and body composition, measured by dual energy X-ray absorptiometry, were analysed together with dietary intake data assessed using an interviewer-based quantitative FFQ. SETTING: Soweto, Johannesburg, South Africa. SUBJECTS: Black, urban South African women were divided into three groups: (i) HIV-negative (HIV-; n 98); (ii) HIV-positive with preserved CD4 counts (HIV+ non-ARV; n 74); and (iii) HIV-positive with low CD4 counts and due to start ARV treatment (HIV+ pre-ARV; n 75). RESULTS: The prevalence of overweight and obesity was high in this population (59 %). The HIV+ pre-ARV group was lighter and had a lower BMI than the other two groups (all P < 0·001). HIV+ pre-ARV women also had lower fat and lean masses and percentage body fat than their HIV- and HIV+ non-ARV counterparts. After adjustment, there were no differences in macronutrient intakes across study groups; however, fat and sugar intakes were high and consumption of predominantly refined food items was common overall. CONCLUSION: HIV-associated immunosuppression may be a key determinant of body composition in HIV-positive women. However, in populations with high obesity prevalence, these differences become evident only at advanced stages of infection.

Calcium and vitamin D metabolism in children in developing countries.

Low dietary calcium intakes and poor vitamin D status are common findings in children living in developing countries. Despite many of the countries lying within the tropics and subtropics, overcrowding, atmospheric pollution, a lack of vitamin D-fortified foods, and social customs that limit skin exposure to sunlight are major factors in the development of vitamin D deficiency. Low dietary calcium intakes are typically observed as a consequence of a diet limited in dairy products and high in phytates and oxalates which reduce calcium bioavailability. Calcium intakes of many children are a third to a half of the recommended intakes for children living in developed countries, yet the consequences of these low intakes are poorly understood as there is limited research in this area. It appears that the body adapts very adequately to these low intakes through reducing renal calcium excretion and increasing fractional intestinal absorption. However, severe deficiencies of either calcium or vitamin D can result in nutritional rickets, and low dietary calcium intakes in association with vitamin D insufficiency act synergistically to exacerbate the development of rickets. Calcium supplementation in children from developing countries slightly increases bone mass, but the benefit is usually lost on withdrawal of the supplement. It is suggested that the major effect of calcium supplementation is on reducing the bone remodelling space rather than structurally increasing bone size or volumetric bone density. Limited evidence from one study raises concerns about the use of calcium supplements in children on habitually low calcium intakes as the previously supplemented group went through puberty earlier and had a final height several centimetres shorter than the controls.

Application of Intervention Mapping to develop a community-based health promotion pre-pregnancy intervention for adolescent girls in rural South Africa: Project Ntshembo (Hope).

BACKGROUND: South Africa (SA) is undergoing multiple transitions with an increasing burden of non-communicable diseases and high levels of overweight and obesity in adolescent girls and women. Adolescence is key to addressing trans-generational risk and a window of opportunity to intervene and positively impact on individuals' health trajectories into adulthood. Using Intervention Mapping (IM), this paper describes the development of the Ntshembo intervention, which is intended to improve the health and well-being of adolescent girls in order to limit the inter-generational transfer of risk of metabolic disease, in particular diabetes risk. METHODS: This paper describes the application of the first four steps of IM. Evidence is provided to support the selection of four key behavioural objectives: viz. to eat a healthy, balanced diet, increase physical activity, reduce sedentary behaviour, and promote reproductive health. Appropriate behaviour change techniques are suggested and a theoretical framework outlining components of relevant behaviour change theories is presented. It is proposed that the Ntshembo intervention will be community-based, including specialist adolescent community health workers who will deliver a complex intervention comprising of individual, peer, family and community mobilisation components. CONCLUSIONS: The Ntshembo intervention is novel, both in SA and globally, as it is: (1) based on strong evidence, extensive formative work and best practice from evaluated interventions; (2) combines theory with evidence to inform intervention components; (3) includes multiple domains of influence (community through to the individual); (4) focuses on an at-risk target group; and (5) embeds within existing and planned health service priorities in SA.

Physical activity and sedentary behavior among adolescents in rural South Africa: levels, patterns and correlates.

BACKGROUND: Physical inactivity is increasing among children and adolescents and may be contributing to the increasing prevalence of overweight and obesity. This study examines physical activity and sedentary behavior patterns, and explores associations with individual, maternal, household, and community factors amongst rural South African adolescents. METHODS: In 2009, 381 subjects, stratified by ages 11-12-years and 14-15-years, were randomly selected from 3511 children and adolescents who had participated in a growth survey two years previously. Weight and height were measured and self-reported Tanner pubertal stage was collected. A questionnaire quantifying frequency and duration of physical activity (PA) domains and sedentary time for the previous 12 months was administered. Moderate-vigorous physical activity (MVPA mins/wk) was calculated for time spent in school and club sport. Socio-demographic and other related data were included from the Agincourt health and socio-demographic system (HDSS). The Agincourt HDSS was established in 1992 and collects prospective data on the community living in the Agincourt sub-district of Mpumalanga Province in rural north-east South Africa. RESULTS: Puberty, maternal education and socio-economic status (SES) contributed significantly to the mulitiple linear regression model for sedentary behavior (R2 = 0.199; adjusted R2 = 0.139; p < 0.000), and sex, SES and maternal education contributed to the tobit regression model for school and club sport MVPA (p < 0.000). MVPA, calculated from school and club sport, was higher in boys than girls (p < 0.001), and informal activity was lower (boys: p < 0.05 and girls: p < 0.01) while sedentary time was higher (girls: p < 0.01) in the older than the younger groups. Ninety-two percent (92%) of the sample reported walking for transport. CONCLUSIONS: In this study of rural South African adolescent boys and girls, SES at the maternal, household and community level independently predicted time spent in sedentary behaviors, and school and club MVPA. This study provides local data that can be used to develop health promotion strategies specific to this community, and other similar communities in developing countries.

Correlating brain volume and callosal thickness with clinical and laboratory indicators of disease severity in children with HIV-related brain disease.

BACKGROUND: Objective MRI markers of central nervous system disease severity may precede subjective features of HIV encephalopathy in children. Previous work in HIV-infected adults shows that brain atrophy was associated with low CD4 and with neuropsychological impairment. Significant thinning of the corpus callosum (CC), predominantly anteriorly, was also found in HIV-infected adults and correlated with CD4 levels. These findings have not been tested in children. PURPOSE: The aim of this study was to determine if brain volume and midsagittal CC linear measurements (thickness and length) on MRI in children with HIV-related brain disease correlate with clinical and laboratory parameters of disease severity. METHODS: Retrospective MRI analysis in children with HIV-related brain disease used a volumetric analysis software and a semi-automated tool to measure brain volume and callosal thickness/length, respectively. Each measure was correlated with clinical parameters of disease severity including Griffiths Mental Development scores (GMDS), absolute CD4 counts (cells/mm(3)), nadir CD4 (the lowest CD4 recorded, excluding baseline), duration of HAART, and decreased brain growth. RESULTS: Thirty-three children with HIV-related brain disease were included. Premotor segment of the CC mean thickness correlated with age (p = 0.394). Motor CC maximum thickness correlated significantly with general developmental quotient (p = 0.0277); CC length correlated with a diagnosis of acquired microcephaly (p = 0.0071) and to CD4 level closest to date of the MRI scan (p = 0.04). CONCLUSIONS: Length of the CC and the "motor CC segment" may represent surrogate clinical biomarkers of central nervous system disease severity and with decreased level of immunity in HIV-infected patients that precede established HIV encephalopathy.

Eating attitudes, body image satisfaction and self-esteem of South African Black and White male adolescents and their perception of female body silhouettes.

This cross-sectional study of urban high schools in Johannesburg, South Africa, sought to examine eating attitudes, body image and self-esteem among male adolescents (n = 391). Anthropometric measurements, Eating Attitudes Test-26 (EAT-26), Rosenberg self-esteem, body image satisfaction and perception of females were collected at age 13, 15 and 17 years. Descriptive analysis was done to describe the sample, and non-parametric Wilcoxon Mann-Whitney test was used to test for significant differences between data that were not normally distributed (EAT-26). Spearman's rank correlation coefficient analyses were conducted to test for associations between self-esteem scores and eating attitudes, body mass indices and body image satisfaction scores. To assess the differences between groups that were normally distributed chi-square tests were carried out. Ethnic differences significantly affected adolescent boys' body mass index (BMI), eating attitudes and self-esteem; White boys had higher self-esteem, BMI and normal eating attitudes than the Black boys did. BMI was positively associated with self-esteem (p = 0.01, r = 0.134) and negatively with dieting behaviour in White boys (p = 0.004, r = -0.257), and with lower EAT-26 bulimic and oral control scores in Black boys. In conclusion, the findings highlight ethnic differences and a need to better understand cultural differences that influence adolescent attitudes and behaviour.

Genetic factors influencing bone mineral content in a black South African population.

Bone mass differs according to ethnic classification, with individuals of African ancestry attaining the highest measurements across numerous skeletal sites. Elevated bone mass is even maintained in those individuals exposed to adverse environmental factors, suggesting a prominent genetic effect that may have clinical or therapeutic value. Using a candidate gene approach, we investigated associations of six candidate genes (ESR1, TNFRSF11A, TNFRSF11B, TNFSF11, SOST and SPP1) with bone mass at the hip and lumbar spine amongst pre-pubertal black South African children (mean age 10.6 years) who formed part of the longitudinal Birth to Twenty cohort. 151 black children were genotyped at 366 polymorphic loci, including 112 previously associated and 254 tagging single nucleotide polymorphisms (SNPs). Linear regression was used to highlight significant associations whilst adjusting for height, weight, sex and bone area. Twenty-seven markers (8 previously associated and 19 tag SNPs; P < 0.05) were found to be associated with either femoral neck (18) or lumbar spine (9) bone mineral content. These signals were derived from three genes, namely ESR1 (17), TNFRSF11B (9) and SPP1 (1). One marker (rs2485209) maintained its association with the femoral neck after correction for multiple testing (P = 0.038). When compared to results amongst Caucasian adults, we detected differences with respect to associated skeletal sites. Allele frequencies and linkage disequilibrium patterns were also significantly different between populations. Hence, our results support the existence of a strong genetic effect acting at the femoral neck in black South African children, whilst simultaneously highlighting possible causes that account for inter-ethnic bone mass diversity.

Investigation into longitudinal dietary behaviours and household socio-economic indicators and their association with BMI Z-score and fat mass in South African adolescents: the Birth to Twenty (Bt20) cohort.

OBJECTIVE: The present study aimed to assess the relationship between dietary habits, change in socio-economic status and BMI Z-score and fat mass in a cohort of South African adolescents. DESIGN: In the longitudinal study, data were collected at ages 13, 15 and 17 years on a birth cohort who have been followed since 1990. Black participants with complete dietary habits data (breakfast consumption during the week and at weekends, snacking while watching television, eating main meal with family, lunchbox use, number of tuck shop purchases, fast-food consumption, confectionery consumption and sweetened beverage consumption) at all three ages and body composition data at age 17 years were included in the analyses. Generalized estimating equations were used to test the associations between individual longitudinal dietary habits and obesity (denoted by BMI Z-score and fat mass) with adjustments for change in socio-economic status between birth and age 12 years. SETTING: Birth to Twenty (Bt20) study, Soweto-Johannesburg, South Africa. SUBJECTS: Adolescents (n 1298; 49·7 % male). RESULTS: In males, the multivariable analyses showed that soft drink consumption was positively associated with both BMI Z-score and fat mass (P < 0·05). Furthermore, these relationships remained the same after adjustment for socio-economic indicators (P < 0·05). No associations were found in females. CONCLUSIONS: Longitudinal soft drink consumption was associated with increased BMI Z-score and fat mass in males only. Fridge ownership at birth (a proxy for greater household disposable income in this cohort) was shown to be associated with both BMI Z-score and fat mass.