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Item Critical value reporting : a survey of 36 clinical laboratories in South Africa(2014-01) Schapkaitz, E.; Mafika, Z.Objective: Critical value policies are used by clinical laboratories to decide when to notify caregivers of life-threatening results. Despite their widespread use, critical value policies have not been published locally. A survey was designed to determine critical value policies for haematology tests in South Africa. Methods: A survey was carried out on 136 identified laboratories across South Africa in January 2013. Of these, 36 responded. Data collected included critical value policies, critical values for haematology parameters, and critical value reporting. Results: Of the 36 laboratories surveyed, 11.1% (n=4) were private, 33.3% (n=12) were affiliated to academic institutions and 55.6% (n=20) were peripheral or regional National Health Laboratory Service laboratories. All the laboratories confirmed that they had a critical value policy, and 83.3% of such policies were derived from local clinical opinion. Mean low and high critical limits for the most frequently listed tests were as follows: haemoglobin <6 and >20 g/dl, platelet count <41 and >1 000 ×109 /l, white cell count <2 and >46×109 /l, activated partial thromboplastin time >101 seconds, and international normalised ratio >6. In almost all cases critical value reporting was performed by the technologist on duty (97.2%). The majority of laboratories required that the person notified of the critical value be the doctor who ordered the test or the caregiver directly involved in the patient’s care (83.3%); 73.3% of laboratories indicated that they followed an algorithm if the doctor/caregiver could not be reached. Conclusion: Each laboratory is responsible for establishing clinically relevant critical limits. Clinicians should be involved in developing the laboratory’s critical value policy. The findings of this survey may be of value to local laboratories that are in the process of establishing or reviewing critical value policiesItem Laboratory information system data demonstrate successful implementation of the prevention of the mother- child transmission programme in South Africa(2014-03) Sherman, G.G.; Lilian, R.R.; Bhardwaj, S.Background: Monitoring the prevention of mother-to-child transmission (PMTCT) programme to identify gaps for early intervention is essential as South Africa progresses from prevention to elimination of HIV infection in children. Early infant diagnosis (EID) by an HIV polymerase chain reaction (PCR) test is recommended at 6 weeks of age for all HIV-exposed infants. The National Health Laboratory Service (NHLS) performs the PCR tests for the public health sector and stores test data in a corporate data warehouse (CDW). Objectives: To demonstrate the utility of laboratory data for monitoring trends in EID coverage and early vertical transmission rates and to describe the scale-up of the EID component of the PMTCT programme. Methods. HIV PCR test data from 2003 to 2012 inclusive were extracted from the NHLS CDW by year, province, age of infant tested and test result and used to calculate EID coverage and early vertical transmission rates to provincial level. Results: Rapid scale-up of EID over the first decade of the PMTCT programme was evident from the 100-fold increase in PCR tests to 350 000 by 2012. In 2012, 73% of the estimated 270 000 HIV-exposed infants requiring an early PCR were tested and the early vertical transmission rate had fallen to 2.4% as a result of successful implementation of the PMTCT programme. Conclusions: Laboratory data can provide real time, affordable monitoring of aspects of the PMTCT programme and assist in achieving virtual elimination of paediatric HIV infection in South Africa.Item National sentinel site surveillance for antimicrobial resistance in Klebsiella pneumoniae isolates in South Africa, 2010-2012(South African Medical Association, 2014-08) Perovic, O.; Singh- Moodley, A.; Duse, A.; Elliott, G.; Bamford, C.; Swe Swe-Han, K.; R Kularatne, R.; Lowman, W.; Whitelaw, A.; Nana, T.; Wadula, J.; Lekalakala, R.; Saif, A.; Marais, E.Background: The increasing rates of antimicrobial resistance observed in the nosocomial pathogen Klebsiella pneumoniae are of major public health concern worldwide. Objectives: To describe the antibiotic susceptibility profiles of K. pneumoniae isolates from bacteraemic patients submitted by sentinel laboratories in five regions of South Africa from mid-2010 to mid-2012. Molecular methods were used to detect the most commonly found extended-spectrum beta lactamase (ESBL) and carbapenemase resistance genes. Methods: Thirteen academic centres serving the public healthcare sector in Gauteng, KwaZulu-Natal, Free State, Limpopo and Western Cape provinces submitted K. pneumoniae isolates from patients with bloodstream infections. Vitek 2 and MicroScan instruments were used for organism identification and susceptibility testing. Multiplex polymerase chain reactions (PCRs) were used to detect blaCTX-M, blaSHV and blaTEM genes in a proportion of the ESBL isolates. All isolates exhibiting reduced susceptibility to carbapenems were PCR tested for blaKPC and blaNDM-1 resistance genes. Results: Overall, 68.3% of the 2 774 isolates were ESBL-positive, showing resistance to cefotaxime, ceftazidime and cefepime. Furthermore, 46.5% of all isolates were resistant to ciprofloxacin and 33.1% to piperacillin-tazobactam. The major ESBL genes were abundantly present in the sample analysed. Most isolates (95.5%) were susceptible to the carbapenems tested, and no isolates were positive for blaKPC or blaNDM-1. There was a trend towards a decrease in susceptibility to most antibiotics. Conclusion: The high proportion of ESBL-producing K. pneumoniae isolates observed, and the prevalence of ESBL genes, are of great concern. Our findings represent a baseline for further surveillance in SA, and can be used for policy and treatment decisions.Item Blood pressure measurements in the ankle are not equivalent to blood pressure measurements in the arm(2014-12) Goldstein, L.N.; Wells, M.; Sliwa, K.Background. Blood pressure (BP) is often measured on the ankle in the emergency department (ED), but this has never been shown to be an acceptable alternative to measurements performed on the arm. Objective. To establish whether the differences between arm and ankle non-invasive BP measurements were clinically relevant (i.e. a difference of ≥10 mmHg). Methods. This was a prospective cross-sectional study in an urban ED making use of a convenience sample of 201 patients (18 - 50 years of age) who were not in need of emergency medical treatment. BP was measured in the supine position on both arms and ankles with the correct size cuff according to the manufacturer’s guidelines. The arm and ankle BP measurements were compared. Results. There was a clinically and statistically significant difference between arm and ankle systolic BP (SBP) and mean arterial pressure (MAP) (–13 mmHg, 95% confidence interval (CI) –28 - 1 mmHg and –5 mmHg, 95% CI –13 - 4 mmHg, respectively), with less difference in diastolic BP (DBP) (2 mmHg, 95% CI –7 - 10 mmHg). Only 37% of SBP measurements and 83% of MAP measurements were within an error range of 10 mmHg, while 95% of DBP measurements agreed within 10 mmHg. While the average differences (or the bias) were generally not large, large variations in individual patients (indicating poor precision) made the prediction of arm BP from ankle measurements unreliable. Conclusion. Ankle BP cannot be used as a substitute for arm BP in the ED.Item Factors influencing access of pregnant women and their infants to their local healthcare system: a prospective, multicentre, observational study(BMC, 2018) Madhi, Shabir A.; Rivera, Luis M.; Sáez-Llorens, Xavier; Menéndez, Clara; Carrim-Ganey, Nazira; Cotton, Mark F.; Katzman, Darren; Luttig, Mariëtha M.; Candelario, Rosalba; Baker, Sherryl; Roychoudhury, MahuaBackground: The successful implementation of maternal vaccination relies on results of clinical trials, considering the prenatal and postnatal attendance at selected healthcare institutions. This study evaluated factors influencing maternal/infant access to healthcare facilities to identify potential barriers to participation in future clinical trials on maternal vaccination. Methods: In this prospective, multi-centre, observational study, pregnant women (N = 3243) were enrolled at ten sites across Panama, the Dominican Republic, South Africa, and Mozambique between 2012 and 2014. They completed questionnaires at enrolment, delivery, and infant follow-up (90 days post-partum) visits, including questions on transportation, phone accessibility, alternative childcare, gestational age at enrolment, delivery location, and health status of their infant. Logistic regression was used to identify factors significantly associated with return to study site for delivery or infant follow-up visits. Results: Among 3229 enrolled women with delivery information, 63.6% (range across sites: 25.3–91.5%) returned to study site for delivery. Older women and those at later gestational age at enrolment were more likely to deliver at the study site. While heterogeneities were observed at site level, shorter travel time at delivery and increased transportation costs at enrolment were associated with increased likelihood of women returning to study site for delivery. Among 3145 women with live-born infants, 3077 (95.3%) provided 90-day follow-up information; of these, 68.9% (range across sites: 25.6–98.9%) returned to study site for follow-up visits. Women with other children and with lower transportation costs at delivery were more likely to return to study site for follow-up visits. Among 666 infants reported sick, 94.3% were taken to a healthcare facility, with only 41.9% (range across sites: 4.9–77.3%) to the study site. Conclusion: Although high retention was observed from enrolment through 90 days after delivery, post-partum surveillance should be broadened beyond the study sites and additional follow-up visits should be planned within the neonatal period. The factors influencing maternal/infant access to healthcare facilities and the issues identified in this study should be taken into consideration in planning future clinical studies on maternal immunisation in low- and middle-income countries.Item 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) 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 cardio-metabolic 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.Item 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 KimBackground: 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.Item Cash transfer interventions for sexual health: meanings and experiences of adolescent males and females in inner-city Johannesburg(BMC, 2018) Khoza, Nomhle; Stadler, Jonathan; MacPhail, Catherine; Chikandiwa, Admire; Brahmbhatt, Heena; Delany-Moretlwe, SineadBackground: In sub-Saharan Africa, there is growing interest in the use of cash transfer (CT) programs for HIV treatment and prevention. However, there is limited evidence of the consequences related to CT provision to adolescents in low-resourced urban settings. We explored the experiences of adolescents receiving CTs to assess the acceptability and unintended consequences of CT strategies in urban Johannesburg, South Africa. Methods: We collected qualitative data during a pilot randomized controlled trial of three CT strategies (monthly payments unconditional vs. conditional on school attendance vs. a once-off payment conditional on a clinic visit) involving 120 adolescents aged 16–18 years old in the inner city of Johannesburg. Interviews were conducted in isiZulu, Sesotho or English with a sub-sample of 49 participants who adhered to study conditions, 6 months after receiving CT (280 ZAR/ 20 USD) and up to 12 months after the program had ended. Interviews were transcribed and translated by three fieldworkers. Codes were generated using an inductive approach; transcripts were initially coded based on emerging issues and subsequently coded deductively using Atlas.ti 7.4. Results: CTs promoted a sense of independence and an adult social identity amongst recipients. CTs were used to purchase personal and household items; however, there were gender differences in spending and saving behaviours. Male participants’ spending reflected their preoccupation with maintaining a public social status through which they asserted an image of the responsible adult. In contrast, female participants’ expenditure reflected assumption of domestic responsibilities and independence from older men, with the latter highlighting CTs’ potential to reduce transactional sexual partnerships. Cash benefits were short-lived, as adolescents reverted to previous behavior after the program’s cessation. Conclusion: CT programs offer adolescent males and females in low-income urban settings a sense of agency, which is vital for their transition to adulthood. However, gender differences in the expenditure of CTs and the effects of ending CT programs must be noted, as these may present potential unintended risks.Item Social health insurance contributes to universal coverage in South Africa, but generates inequities: survey among members of a government employee insurance scheme(BMC, 2018) Goudge, Jane; Harris, Bronwyn; Nxumalo, Nonhlanhla; Chersich, Matthew F.; Alaba, Olufunke A.; Govender, VeloshneeBackground: Many low- and middle-income countries are reforming their health financing mechanisms as part of broader strategies to achieve universal health coverage (UHC). Voluntary social health insurance, despite evidence of resulting inequities, is attractive to policy makers as it generates additional funds for health, and provides access to a greater range of benefits for the formally employed. The South African government introduced a voluntary health insurance scheme (GEMS) for government employees in 2005 with the aim of improving access to care and extending health coverage. In this paper we ask whether the new scheme has assisted in efforts to move towards UHC. Methods: Using a cross-sectional survey across four of South Africa’s nine provinces, we interviewed 1329 government employees, from the education and health sectors. Data were collected on socio-demographics, insurance coverage, health status and utilisation of health care. Multivariate logistic regression was used to determine if service utilisation was associated with insurance status. Results: A quarter of respondents remained uninsured, even higher among 20–29 year olds (46%) and lower-skilled employees (58%). In multivariate analysis, the odds of an outpatient visit and hospital admission for the uninsured was 0.3 fold that of the insured. Cross-subsidisation within the scheme has provided lower-paid civil servants with improved access to outpatient care at private facilities and chronic medication, where their outpatient (0.54 visits/ month) and inpatient utilisation (10.1%/year) approximates that of the overall population (29.4/month and 12.2% respectively). The scheme, however, generated inequities in utilisation among its members due to its differential benefit packages, with, for example, those with the most benefits having 1.0 outpatient visits/month compared to 0.6/ month with lowest benefits. Conclusions: By introducing the scheme, the government chose to prioritise access to private sector care for government employees, over improving the availability and quality of public sector services available to all. Government has recently regained its focus on achieving UHC through the public system, but is unlikely to discontinue GEMS, which is now firmly established. The inequities generated by the scheme have thus been institutionalised within the country’s financing system, and warrant attention. Raising scheme uptake and reducing differentials between benefit packages will ameliorate inequities within civil servants, but not across the country as a whole.Item 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.Item The importance of morphological identification of African anopheline mosquitoes (Diptera: Culicidae) for malaria control programmes(BioMed Central (BMC), 2018-01) Erlank, Erica; Koekemoer, Lizette L.; Coetzee, MaureenBackground: 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.Item Molecular and physiological analysis of Anopheles funestus swarms in Nchelenge, Zambia(BMC, 2018-01) Zawada, Jacek W.; Dahan‑Moss, Yael L.; Muleba, Mbanga; Dabire, Roch K.; Maïga, Hamid; Venter, Nelius; Davies, Craig; Hunt, Richard H.; Coetzee, Maureen; Koekemoer, Lizette L.Background: Anopheles funestus has been recognized as a major malaria vector in Africa for over 100 years, but knowledge on many aspects of the biology of this species is still lacking. Anopheles funestus, as with most other anophelines, mate through swarming. A key event that is crucial for the An. funestus male to mate is genitalia rotation. This involves the 135° to 180° rotation of claspers, which are tipped with claws. This physical change then enables the male to grasp the female during copulation. The aim of this investigation was to molecularly characterize wild An. funestus swarms from Zambia and examine the degree of genitalia rotation within the swarm. Methods: Anopheles funestus swarms were collected from Nchelenge, northern Zambia, during dusk periods in May 2016. All the adults from the swarm were analysed morphologically and identified to species level using a multiplex PCR assay. Anopheles funestus s.s. specimens were molecularly characterized by restriction fragment length polymorphism type and Clade type assays. The different stages of genitalia rotation were examined in the adult males. Results: A total of six swarms were observed during the study period and between 6 and 26 mosquitoes were caught from each swarm. Species analysis revealed that 90% of the males from the swarms were An. funestus s.s. MWtype, with 84% belonging to clade I compared to 14% clade II and 2% failed to amplify. Very few specimens (3.4%) were identified as Anopheles gambiae s.s. Eighty percent of the males from the swarm had complete genitalia rotation. Conclusions: This is the first time that An. funestus swarms have been molecularly identified to species level. Anopheles funestus swarms appear to be species-specific with no evidence of clade-type differentiation within these swarms. The An. funestus swarms consist mainly of males with fully rotated genitalia, which strongly suggests that swarming behaviour is triggered primarily when males have matured.Item 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.Item Perceptions of counsellors and youth-serving professionals about sexual and reproductive health services for adolescents in Soweto, South Africa(BMC, 2018-02) Mulaudzi, Mamakiri; Dlamini, Busisiwe Nkala; Coetzee, Jenny; Sikkema, Kathleen; Gray, Glenda; Dietrich, Jana JanineBackground: Adolescents in South Africa remain vulnerable to HIV. Therefore, it is crucial to provide accessible adolescent-friendly HIV prevention interventions that are sensitive to their needs. This study aimed to investigate the perceptions of HIV counsellors and other youth-serving professionals about the barriers to providing adolescent youth-friendly sexual and reproductive health services to adolescents in Soweto, South Africa. The study also explored how sexual and reproductive health services in South Africa could be improved to become more accessible to adolescents. Methods: The research team conducted two focus group discussions with HIV counsellors, and 19 semi-structured interviews with youth-serving professionals from organisations working with adolescents. Audio-recorded data were transcribed verbatim and analysed using thematic analysis. Results: The results of the study reveal that counsellors were expected to give adolescents HIV counselling and testing (HCT) but felt restricted by what they perceived as inflexible standard operating procedures. Counsellors reported inadequate training to address adolescent psychosocial issues during HCT. Healthcare provider attitudes were perceived as a barrier to adolescents using sexual and reproductive health services. Participants strongly recommended augmenting adolescent sexual and reproductive health services to include counsellors and adolescents in developing age- and context-specific HIV prevention services for adolescents. Conclusion: Continuous upskilling of HIV counsellors is a critical step in providing adolescent-friendly services.Item Influence of vitamin D receptor polymorphisms on biochemical markers of mineral bone disorders in South African patients with chronic kidney disease(2018-02) Waziri, Bala; Dix-Peek, Therese; Dickens, Caroline; Duarte, Raquel; Naicker, SaraladeviBackground: It remains unclear whether genetic factors may explain the reported variation in the levels of biochemical markers of chronic kidney disease mineral and bone disorders (CKD- MBD) across ethnic groups. Therefore, the aim of this study was to examine the influence of vitamin D receptor (VDR) polymorphisms on secondary hyperparathyroidism and its association with vitamin D levels in black and white South African study participants. Methods: This was a cross sectional study involving 272 CKD stage 3- 5D patients and 90 healthy controls. The four major VDR polymorphisms (Bsm 1, Fok 1, Taq 1, and Apa1) were genotyped using the polymerase chain reaction- restriction fragment length polymorphism (PCR –RFLP) method. In addition, biochemical markers of CKD-MBD were measured to determine their associations with the four VDR polymorphisms. Results: With the exception of Taq I polymorphism, the distribution of the VDR polymorphisms differed significantly between blacks and whites. In hemodialysis patients, the Bb genotype was significantly associated with moderate secondary hyperparathyroidism (OR, 3.88; 95 CI 1.13–13.25, p = 0.03) and severe hyperparathyroidism (OR, 2.54; 95 CI 1.08–5.96, p = 0.03). This was consistent with the observed higher levels of median parathyroid hormone, fibroblast growth factor 23 and mean phosphate in patients with Bb genotype. This candidate risk genotype (Bb) was over represented in blacks compared to whites (71.0% versus 55.6%, p < 0.0001). In an unadjusted regression model, FokFf genotype was found to be significantly associated with the risk of developing severe vitamin D deficiency < 15 ng/ml (OR, 1.89; 95 CI 1.17–3.07, p = 0.01). Conclusion: The VDR Bb genotype is an independent predictor of developing secondary hyperparathyroidism in patients with end stage kidney disease. In addition, study participants with FokFf genotype are at increased of developing severe 25 -hydroxyvitamin D [25(OH)D] deficiency.Item 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, ChristineBackground: 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.Item Neurodevelopmental assessment of HIV-exposed uninfected and early-treated HIV-infected children: study protocol(BMC, 2018-04) Strehlau, Renate; van Aswegen, Tamryn; Potterton, JoanneObjective: 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.Item 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, ImmoBackground: 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.Item Aqueous extract of moringa (Moringa oleifera) leaf (AEMOL) on the growth, sensory and histology parameters of broiler chickens(ALÖKI Kft, 2020-07) Mbajiorgu, Ejikeme F.; Alabi, O. J.; Ng’Ambi, J. W.A completely randomized design experiment was used to determine the effects of aqueous extract of Moringa oleifera leaf (AEMOL) on growth, sensory and histology parameters of broiler chickens. Treatment 1 served as the control (antibiotics), Treatment two was given ordinary water (AEMOL0). Treatments 3, 4, 5 and 6 contained 30, 60, 90 and 120 ml of AEMOL per litre of water per day, respectively. Data obtained were analyzed using one-way analysis of variance and mean separation was done using Duncan’s test for multiple comparisons. Results showed that the extract influenced (P < 0.05) the feed intake and water intake at the broiler starter phase WHILE birds on the control diet had higher values. Finisher phase results showed that final weight, weight gain, feed intake, FCR and water intake were influenced (P < 0.05) by the extract with birds treated with 60 ml/l of AEMOL doing better for most parameters except the FCR. All the digestibility and sensory parameters measured were also influenced (P < 0.05) by the extract. However, histological parameters measured were not affected (P > 0.05) by the extract. It could be concluded that the extract inclusion levels up to 90 ml/l can be used to replace antibiotic growth promoter without compromising the advantages of antibiotic growth promoter.Item Tamoxifen induces hypercoagulation and alterations in ERα and ERβ dependent on breast cancer sub‑phenotype ex vivo(Nature, 2020-11-06) Pather, Kyrtania; Augustine, T. N.Tamoxifen shows efficacy in reducing breast cancer-related mortality but clinically, is associated with increased risk for thromboembolic events. We aimed to determine whether breast tumour subphenotype could predict propensity for thrombosis. We present two ex vivo Models of Tamoxifentherapy, Model 1 in which treatment recapitulates accumulation within breast tissue, by treating MCF7 and T47D cells directly prior to exposure to blood constituents; and Model 2 in which we recreate circulating Tamoxifen by treating blood constituents prior to exposure to cancer cells. Blood constituents included whole blood, platelet-rich plasma and platelet-poor plasma. Hypercoagulation was assessed as a function of thrombin activity, expression of CD62P and CD63 activation markers defined as an index of platelet activation, and platelet morphology; while oestrogen receptor expression was assessed using immunocytochemistry with quantitative analysis. We determined, in concert with clinical studies and contrary to selected laboratory investigations, that Tamoxifen induces hypercoagulation, dependent on sub-phenotypes, with the T47D cell line capacity most enhanced. We determined a weak positive correlation between oestrogen receptor expression, and CD62P and CD63; indicating an association between tumour invasion profiles and hypercoagulation, however, other yet unknown factors may play a predictive role in defining hypercoagulation.