Faculty of Health Sciences (Research Outputs)

Permanent URI for this communityhttps://hdl.handle.net/10539/37788

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Start date: 2014End date: 2018

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    Neurodevelopmental assessment of HIV-exposed uninfected and early-treated HIV-infected children: study protocol
    (BioMed Central, 2018-04) Strehlau, Renate; van Aswegen, Tamryn; Potterton, Joanne
    Objective: Sub-Saharan Africa has the highest prevalence of children at risk of not achieving their developmental potential, attributable largely to the human immunodefciency virus (HIV) pandemic coupled with negative environmental factors. Childhood developmental stimulation programmes can mitigate adverse outcomes. Methods: Neonates testing HIV positive at birth will be initiated on antiretroviral treatment (ART) and receive an ageappropriate stimulation program, updated at 3 monthly intervals through the frst year of life. Neurodevelopment at 12 months of age will be assessed using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Outcomes will be compared with HIV-infected and HIV-exposed uninfected children (HEU) not having received the stimulatory intervention. Associations between neurodevelopmental outcomes, environmental factors, and parental stress will be investigated. The study will take place at a single site in Johannesburg, South Africa. This non-randomised controlled intervention study, with a single non-blinded comparative intervention group, aims to investigate whether an early childhood stimulation programme used in conjunction with ART initiated at birth can positively impact neurodevelopmental outcomes at 1 year of age in children infected with HIV.
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    Assessing runs of Homozygosity: a comparison of SNP Array and whole genome sequence low coverage data
    (BMC, 2018-01) Ceballos, Francisco C.; Hazelhurst, Scott; Ramsay, Michèle
    Background: Runs of Homozygosity (ROH) are genomic regions where identical haplotypes are inherited from each parent. Since their first detection due to technological advances in the late 1990s, ROHs have been shedding light on human population history and deciphering the genetic basis of monogenic and complex traits and diseases. ROH studies have predominantly exploited SNP array data, but are gradually moving to whole genome sequence (WGS) data as it becomes available. WGS data, covering more genetic variability, can add value to ROH studies, but require additional considerations during analysis. Results: Using SNP array and low coverage WGS data from 1885 individuals from 20 world populations, our aims were to compare ROH from the two datasets and to establish software conditions to get comparable results, thus providing guidelines for combining disparate datasets in joint ROH analyses. By allowing heterozygous SNPs per window, using the PLINK homozygosity function and non-parametric analysis, we were able to obtain non-significant differences in number ROH, mean ROH size and total sum of ROH between data sets using the different technologies for almost all populations. Conclusions: By allowing 3 heterozygous SNPs per ROH when dealing with WGS low coverage data, it is possible to establish meaningful comparisons between data using SNP array and WGS low coverage technologies
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    The effect of a ketogenic diet versus a high-carbohydrate, low-fat diet on sleep, cognition, thyroid function, and cardiovascular health independent of weight loss: study protocol for a randomized controlled trial
    (BMC, 2018-01) Iacovides, Stella; Meiring, Rebecca M.
    Background: Many physiological health benefits observed after following a ketogenic diet (KD) can be attributed to the associated weight loss. The KD has become more prominent as a popular health choice, not only in obese/ overweight individuals, but also in healthy adults. The study aims to determine the effects of a KD, independent of weight loss, on various aspects of physiological health including: sleep, thyroid function, cognition, and cardiometabolic health. The study will also aim to determine whether a change in basal metabolic rate may be associated with any changes observed. Methods: Twenty healthy men and women between 18 and 50 years of age will take part in this study. In a randomized controlled, cross-over design, participants will follow two isocaloric diets: a high-carbohydrate, low-fat diet (55% CHO, 20% fat, 25% protein) and a KD (15% CHO, 60% fat, 25% protein). Each dietary intervention will last for a minimum of 3 weeks, with a 1-week washout period in between. Before and after each diet, participants will be assessed for sleep quality, cognitive function, thyroid function, and basal metabolic rate. A blood sample will also be taken for the measurement of cardio-metabolic and immune markers. Discussion: The present study will help in understanding the potential effects of a KD on aspects of physiological health in healthy adults, without the confounding factor of weight loss. The study aims to fill a significant void in the academic literature with regards to the benefits and/or risks of a KD in a healthy population, but will also explore whether diet-related metabolic changes may be responsible for the changes observed in physiological health.
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    The importance of morphological identification of African anopheline mosquitoes (Diptera: Culicidae) for malaria control programmes
    (BMC, 2018-01) Erlank, Erica; Koekemoer, Lizette L.; Coetzee, Maureen
    Background: The correct identification of disease vectors is the first step towards implementing an effective control programme. Traditionally, for malaria control, this was based on the morphological differences observed in the adults and larvae between different mosquito species. However, the discovery of species complexes meant that genetic tools were needed to separate the sibling species and today there are standard molecular techniques that are used to identify the two major malaria vector groups of mosquitoes. On the assumption that species-diagnostic DNA polymerase chain reaction (PCR) assays are highly species-specific, experiments were conducted to investigate what would happen if non-vector species were randomly included in the molecular assays. Methods: Morphological keys for the Afrotropical Anophelinae were used to provide the a priori identifications. All mosquito specimens were then subjected to the standard PCR assays for members of the Anopheles gambiae complex and Anopheles funestus group. Results: One hundred and fifty mosquitoes belonging to 11 morphological species were processed. Three species (Anopheles pretoriensis, Anopheles rufipes and Anopheles rhodesiensis) amplified members of the An. funestus group and four species (An. pretoriensis, An. rufipes, Anopheles listeri and Anopheles squamosus) amplified members of the An. gambiae complex. Conclusions: Morphological identification of mosquitoes prior to PCR assays not only saves time and money in the laboratory, but also ensures that data received by malaria vector control programmes are useful for targeting the major vectors.
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    Predictors of switch to and early outcomes on third-line antiretroviral therapy at a large public-sector clinic in Johannesburg, South Africa
    (BMC, 2018) Evans, Denise; Hirasen, Kamban; Berhanu, Rebecca; Malete, Given; Ive, Prudence; Spencer, David; Badal‑Faesen, Sharlaa; Sanne, Ian M.; Fox, Matthew P.
    Background: While efficacy data exist, there are limited data on the outcomes of patients on third-line antiretroviral therapy (ART) in sub-Saharan Africa in actual practice. Being able to identify predictors of switch to third-line ART will be essential for planning for future need. We identify predictors of switch to third-line ART among patients with significant viraemia on a protease inhibitor (PI)-based second-line ART regimen. Additionally, we describe characteristics of all patients on third-line at a large public sector HIV clinic and present their early outcomes. Methods: Retrospective analysis of adults (≥ 18 years) on a PI-based second-line ART regimen at Themba Lethu Clinic, Johannesburg, South Africa as of 01 August 2012, when third-line treatment became available in South Africa, with significant viraemia on second-line ART (defined as at least one viral load ≥ 1000 copies/mL on second-line ART after 01 August 2012) to identify predictors of switch to third-line (determined by genotype resistance testing). Third line ART was defined as a regimen containing etravirine, raltegravir or ritonavir boosted darunavir, between August 2012 and January 2016. To assess predictors of switch to third-line ART we used Cox proportional hazards regression among those with significant viraemia on second-line ART after 01 August 2012. Then among all patients on third-line ART we describe viral load suppression, defined as a viral load < 400 copies/mL, after starting third-line ART. Results: Among 719 patients in care and on second-line ART as of August 2012 (with at least one viral load ≥ 1000 copies/mL after 01 August 2012), 36 (5.0% over a median time of 54 months) switched to third-line. Time on second-line therapy (≥ 96 vs. < 96 weeks) (adjusted Hazard Ratio (aHR): 2.53 95% CI 1.03–6.22) and never reaching virologic suppression while on second-line ART (aHR: 3.37 95% CI 1.47–7.73) were identified as predictors of switch. In a separate cohort of patients on third-line ART, 78.3% (47/60) and 83.3% (35/42) of those in care and with a viral load suppressed their viral load at 6 and 12 months, respectively. Conclusions: Our results show that the need for third-line is low (5%), but that patients’ who switch to third-line ART have good early treatment outcomes and are able to suppress their viral load. Adherence counselling and resistance testing should be prioritized for patients that are at risk of failure, in particular those who never suppress on second line and those who have been on PI-based regimen for extended periods.
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    Bone mineral density in midlife long-term users of hormonal contraception in South Africa: relationship with obesity and menopausal status
    (BMC, 2018-04) Beksinska, Mags E.; Smit, Jenni A.; Kleinschmidt, Immo
    Background: In South Africa, hormonal contraception is widely used in women over the age of 40 years. One of these methods and the most commonly used is depot-medroxyprogesterone acetate (DMPA) which has been found to have a negative effect on bone mass. Limited information is available on the effect of norethisterone enanthate (NET-EN) on bone mass, and combined oral contraceptives (COCs) have not been found to be associated with loss of bone mass. The aim of this study was to investigate bone mineral density (BMD) in pre and perimenopausal women (40–49 years) in relation to use of DMPA, NET-EN and COCs for at least 12 months preceding recruitment into the study and review associations with body mass index (BMI) and menopausal status. Methods: One hundred and twenty seven users of DMPA, 102 NET-EN users and 106 COC users were compared to 161 nonuser controls. Menopausal status was assessed, BMI and forearm BMD was measured at the distal radius using dual X-ray absorptiometry. Comparison analysis was conducted at baseline and 2.5 years. Results: There was no significant difference in BMD between the four contraceptive user groups (p = 0.26) with and without adjustment for age at baseline or at 2.5 years (p = 0.52). The BMD was found to be significantly associated with BMI (p = < 0.0001) with an increase of one unit of BMI translating to an increase of 0.0044 g/cm2 in radius BMD. Follicle stimulating hormone (FSH) level ≥ 25.8 mIU/mL was associated with a decrease of 0.017 g/cm2 in radius BMD relative to women with FSH < 25.8 mIU/mL. Significant interaction between FSH and BMI in their effect on BMD was observed (p = .006). Conclusion: This study found no evidence that long-term use of DMPA, NET-EN and COCs affects forearm BMD in this population at baseline or after 2.5 years of follow-up. This study also reports the complex relationship and significant interaction between FSH and BMI in their effect on BMD. BMD research in older women needs to ensure that women are assessed for menopausal status and BMI.
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    Neurodevelopmental assessment of HIV-exposed uninfected and early-treated HIV-infected children: study protocol
    (BMC, 2018-04) Strehlau, Renate; van Aswegen, Tamryn; Potterton, Joanne
    Objective: Sub-Saharan Africa has the highest prevalence of children at risk of not achieving their developmental potential, attributable largely to the human immunodeficiency virus (HIV) pandemic coupled with negative environmental factors. Childhood developmental stimulation programmes can mitigate adverse outcomes. Methods: Neonates testing HIV positive at birth will be initiated on antiretroviral treatment (ART) and receive an age appropriate stimulation program, updated at 3 monthly intervals through the first year of life. Neurodevelopment at 12 months of age will be assessed using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Outcomes will be compared with HIV-infected and HIV-exposed uninfected children (HEU) not having received the stimulatory intervention. Associations between neurodevelopmental outcomes, environmental factors, and parental stress will be investigated. The study will take place at a single site in Johannesburg, South Africa. This non-randomised controlled intervention study, with a single non-blinded comparative intervention group, aims to investigate whether an early childhood stimulation programme used in conjunction with ART initiated at birth can positively impact neurodevelopmental outcomes at 1 year of age in children infected with HIV.
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    The relationship between childhood adversity, recent stressors, and depression in college students attending a South African university
    (BMC, 2018-03) Mall, Sumaya; Mortier, Philippe; Taljaard, Lian; Roos, Janine; Stein, Dan J. Stein; Lochner, Christine
    Background: College students are at risk of depression. This risk may be increased by the experience of childhood adversity and/or recent stressors. This study examined the association between reported experiences of childhood adversity, recent stressors and depression during the last 12 months in a cohort of South African university students. Methods: Six hundred and eighty-six first year students at Stellenbosch University in South Africa completed a health focused e-survey that included items on childhood adversity, recent stressors and mood. Individual and population attributable risk proportions (PARP) between experiences of childhood adversity and 12-month stressful experiences and 12-month depression were estimated using multivariate binomial logistic regression analysis. Results: About one in six students reported depression during the last 12 months. Being a victim of bullying and emotional abuse or emotional neglect during childhood were the strongest predictors of depression in the past year at both individual and population level. With regard to recent stressors, a romantic partner being unfaithful, serious ongoing arguments or break-ups with some other close friend or family member and a sexual or gender identity crisis were the strongest predictors of depression. The predictor effect of recent stressors was significantly reduced in the final model that adjusted for the type and number of childhood traumatic experiences. At a population level, academic stress, serious ongoing arguments or break-ups with a close friend or family member, and serious betrayal by someone close were the variables that yielded the highest PARP. Conclusions: Our findings suggest a significant relationship between early adversity, recent stressors, and depression here and throughout, consistent with the broader literature on predictors of depression. This study contributes to the limited data on college students’ mental health in low and middle income countries including on the African continent. The findings provide information on the population level effect sizes of trauma as a risk factor for depression, as well as on the relationship between specific recent stressors and depression in college students.
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    Development and feasibility of a wearable infant wrist band for the objective measurement of physical activity using accelerometery
    (BMC, 2018) Prioreschi, Alessandra; Nappey, Thomas; Westgate, Kate; Olivier, Patrick; Brage, Soren; Micklesfield, Lisa Kim
    Background: It is important to be able to reliably and feasibly measure infant and toddler physical activity in order to determine adherence to current physical activity guidelines and effects on early life development, growth and health. This study aimed to describe the development of an infant wearable wrist-worn band for the measurement of physical activity; to determine the feasibility of the device data for observational measurement of physical activity and to determine the caregiver reported acceptability of the infant wearable wrist band. Methods: After various iterations of prototypes and piloting thereof, a final wearable band was designed to fit an Axivity AX3 monitor. Mother and infant/toddler (aged 3–24 months) pairs (n = 152) were recruited, and mothers were asked for their child to wear the band with enclosed monitor at all times for 1 week (minimum 3 days). Feasibility was assessed by determining technical reliability of the data, as well as wear time and compliance according to requirements for observational measurement. Acceptability was assessed via questionnaire. Results: Technical reliability of the Axivity AX3 monitors in this age group was good. After excluding days that did not have at least 15 h of wear time, only 2% of participants had less than three valid days of data remaining, and 4% of participants had no data (due to device loss or data loss). Therefore, 94% of participants were compliant, having three or more days of wear with at least 15 h of wear per day, thus providing enough valid data for observational measurement. The majority (60%) of mothers reported being “very happy” with the safety of the device, while only 8% were “a little worried”. A large majority (86%) of mothers stated that the band attracted attention from others, although this was mostly attributed to curiosity about the function of the band. Most (80%) of participants rated the comfort of the band as “comfortable”, and 10% rated it as “very comfortable”. Conclusions: The infant wearable band proved to be feasible and acceptable according to the criteria tested, and compliance wearing the band was good. We have therefore provided a replicable, comfortable and acceptable pearable band for the measurement of infant and toddler physical activity.
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    The presence of occipital hair in the pilonidal sinus cavity—a triple approach to proof
    (Springer, 2018-02) Doll, Dietrich; Bosche, F.; Hauser, A.; Moersdorf, P.; Sinicina, I.; Grunwald, J.; Reckel, F.; Luedi, M. M.
    Purpose: Hair in the pilonidal sinus is not growing within the sinus cavity, as hair follicles are not present there. Not few pilonidal patients do not have intergluteal hair, which is said to be the causative agent of folliculitis and pilonidal genesis. So, what is the real source of the hair forming the typical pilonidal hair nest? Methods: A trifold approach was used: First, axial hair strength testing of pilonidal hair and body hair harvested from head, lower back (glabella sacralis), and cranial third of intergluteal fold. Hair strength match was compared clinically. Second, comparative morphological examination by expert forensic biologist of hair from sinus and dorsal body hair. Third, statistical Bayesian classification of every single sinus hair based on its strength was done to determine the most probable region of origin. Results: Using clinical hair strength comparison, in 13/20 patients, head hair is the stiffest hair, followed by intergluteal hair. Only in 6/20 patients, this is the case with hair from the glabella sacralis. According to comparative morphological comparison, a minimum of 5 of 13 hair nests with possible hair allocation examined contain hair from the occiput. In 5/18 nests, hair could not be determined to a specific location though. Statistical classification with correction for multiple testing shows that 2 nests have hair samples that are at least 100 times more probable to originate from head or lower back than from intergluteal fold. Conclusion: We saw our null hypothesis that hair in the sinus cavity is from the intergluteal region^ rejected by each of three different approaches. There is strong evidence that occipital hair is present regularly in pilonidal sinus nests. We should start thinking of occipital hair as an important hair source for the development of the pilonidal hair nest.