1. Academic Wits Research Publications (Faculties submissions)

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Characterization of putative DD-carboxypeptidase-encoding genes in Mycobacterium smegmatis
(Nature Research, 2019-03) Ealand, Christopher S.; Asmal, Rukaya; Mashigo, Lethabo; Campbell, Lisa; Kana, Bavesh D.
Penicillin binding proteins (PBPs) are the target of numerous antimicrobial agents that disrupt bacterial cell wall synthesis. In mycobacteria, cell elongation occurs through insertion of nascent cell wall material in the sub-polar region, a process largely driven by High Molecular Weight PBPs. In contrast, the function of DD-carboxypeptidases (DD-CPases), which are Low Molecular Weight Class 1C PBPs, in mycobacteria remains poorly understood. Mycobacterium smegmatis encodes four putative DD-CPase homologues, which display homology to counterparts in Escherichia coli. Herein, we demonstrate that these are expressed in varying abundance during growth. Deletion of MSMEG_1661, MSMEG_2433 or MSMEG_2432, individually resulted in no defects in growth, cell morphology, drug susceptibility or spatial incorporation of new peptidoglycan. In contrast, deletion of MSMEG_6113 (dacB) was only possible in a merodiploid strain expressing the homologous M. tuberculosis operon encoding Rv3627c (dacB), Rv3626c, Rv3625c (mesJ) and Rv3624c (hpt), suggestive of essentiality. To investigate the role of this operon in mycobacterial growth, we depleted gene expression using anhydrotetracyclineresponsive repressors and noted reduced bipolar peptidoglycan synthesis. These data point to a possible role for this four gene operon, which is highly conserved across all mycobacterial species, in regulating spatial localization of peptidoglycan synthesis.
Hypertension in a rural community in South Africa: what they know, what they think they know and what they recommend
(BioMed Central, 2019-03) Klipstein-Grobusch, Kerstin; Jongen, Vita W.; Lalla-Edward, Samanta T.; Vos, Alinda G.; Godijk, Noortje G.; Tempelman, Hugo; Grobbee, Diederick E.; Devillé, Walter
Background: Hypertension is one of the most important risk factors for cardiovascular disease and has a high prevalence in South Africa and other low- and middle-income countries. However, awareness of hypertension has been reported to be low. Health programmes can increase awareness of hypertension and its causes, but hinge on the knowledge and perception of the targeted community. Therefore, this study investigated knowledge on and perceptions about hypertension of community members in a rural area in Limpopo, South Africa with the aim to increase awareness of hypertension and cardiovascular disease in the local population. Methods: Using a mixed methods study approach, 451 participants of the Ndlovu Cohort Study, attending a follow-up visit between August 2017 and January 2018, completed a questionnaire on cardiovascular risk perception. A knowledge score was calculated for all participants. Sixty participants were invited to participate in six focus group discussions, of which 56 participated. Audio recordings were transcribed verbatim, transcripts coded, and thematic analysis of the data undertaken to obtain an understanding of knowledge and perception of hypertension in the community. Results: Most members of the community seemed to have intermediate (74.3%) or good (14.0%) knowledge of hypertension based on the knowledge score, and only 11.8% of the population had poor knowledge. The risk factors of hypertension seemed to be well known in the community. Poverty was identified as a major vulnerability in this community limiting choices for healthy lifestyles such as nutritious foods, recreational physical activity and accessing health care timely. Participants proposed community-based activities as an effective way to reach out to community members for prevention and management of hypertension. Conclusion: This study highlights the need for improved health promotion efforts to increase knowledge of hypertension in rural communities, and to address poverty as a major obstacle to healthy life-style choices.
Increases in statin eligibility to reduce cardiovascular risk according to the 2013 ACC/AHA cholesterol guidelines in the Africa Middle East region: a sub-analysis of the Africa Middle East Cardiovascular Epidemiological (ACE) study
(BioMed Central, 2019-03) Raal, Frederick J.; Hamoui, Omar; Omar, Mohamed I.; Rashed, Wafa; Kane, Abdoul; Alami, Mohamed; Abreu, Paula; Mashhoud, Walid; Alsheikh-Ali, Alawi A.
Background: With development of cholesterol management guidelines by the American College of Cardiology/ American Heart Association (ACC/AHA), more individuals at risk of cardiovascular disease may be eligible for statin therapy. It is not known how this affects statin eligibility in the Africa and Middle East Region. Methods: Data were used from the Africa Middle East Cardiovascular Epidemiological (ACE) study. The percentage of subjects eligible for statins per the ACC/AHA 2013 cholesterol guidelines and the 2002 National Cholesterol Education Program-Adult Treatment Panel (NCEP-ATP III) recommendations were compared. Analyses were carried out according to age, gender, community (urban/rural), and country income categories based on World Bank definitions. Results: According to the ACC/AHA recommendations, 1695 out of 4378 subjects (39%; 95% confidence interval [CI], 37–40%) satisfied statin eligibility criteria vs. 1043/4378 (24%; 95% CI, 23–25%) per NCEP-ATP recommendations, representing a 63% increase in statin eligibility. Consistent increases in eligibility for statin therapy were seen according to the ACC/AHA vs. NCEP-ATP guidelines across sub-groups of age, gender, community, and country income. Notable increases for statin eligibility according to ACC/AHA vs. NCEP-ATP were seen, respectively, in subjects aged ≥65 years (86% vs. 39%), in males (46% vs. 25%), in low-income countries (28% vs. 14%), and rural communities (37% vs. 19%). Conclusion: An increase in statin eligibility was seen applying ACC/AHA cholesterol guidelines compared with previous NCEP-ATP recommendations in the Africa Middle East region. The economic consequences of these guideline recommendations will need further research.
A tunable Josephson platform to explore many-body quantum optics in circuit-QED
(Nature Research, 2019-02) Snyman, Izak; Martínez, Javier Puertas; Léger, Sébastien; Gheeraert, Nicolas; Dassonneville, Rémy; Planat, Luca; Foroughi, Farshad; Krupko, Yuriy; Buisson, Olivier; Naud, Cécile; Hasch-Guichard, Wiebke; Florens, Serge; Roch, Nicolas
The interaction between light and matter remains a central topic in modern physics despite decades of intensive research. Coupling an isolated emitter to a single mode of the electromagnetic field is now routinely achieved in the laboratory, and standard quantum optics provides a complete toolbox for describing such a setup. Current efforts aim to go further and explore the coherent dynamics of systems containing an emitter coupled to several electromagnetic degrees of freedom. Recently, ultrastrong coupling to a transmission line has been achieved where the emitter resonance broadens to a significant fraction of its frequency, and hybridizes with a continuum of electromagnetic (EM) modes. In this work we gain significantly improved control over this regime. We do so by combining the simplicity and robustness of a transmon qubit and a bespoke EM environment with a high density of discrete modes, hosted inside a superconducting metamaterial. This produces a unique device in which the hybridisation between the qubit and many modes (up to ten in the current device) of its environment can be monitored directly. Moreover the frequency and broadening of the qubit resonance can be tuned independently of each other in situ. We experimentally demonstrate that our device combines this tunability with ultrastrong coupling and a qubit nonlinearity comparable to the other relevant energy scales in the system. We also develop a quantitative theoretical description that does not contain any phenomenological parameters and that accurately takes into account vacuum fluctuations of our large scale quantum circuit in the regime of ultrastrong coupling and intermediate non-linearity. The demonstration of this new platform combined with a quantitative modelling brings closer the prospect of experimentally studying many-body effects in quantum optics. A limitation of the current device is the intermediate nonlinearity of the qubit. Pushing it further will induce fully developed many-body effects, such as a giant Lamb shift or nonclassical states of multimode optical fields. Observing such effects would establish interesting links between quantum optics and the physics of quantum impurities
Retention of health care workers at health facility, trends in the retention of knowledge and correlates at 3rd year following training of health care workers on the prevention of mother-to-child transmission (PMTCT) of HIV–National Assessment
(BioMed Central, 2019-01) Kufe, Nyuyki Clement; Metekoua, Carole; Nelly, Monkam; Tumasang, Florence; Mbu, Enow Robinson
Background: Knowledgeable Health Care Workers (HCWs) are indispensable for the proper management of clients. We investigated retention of HCWs at health facility and retention of knowledge at 18, 24 and 36 months after training and correlates for retention of knowledge at 3rd year. Methods: A cross-sectional study was conducted among 1000 HCWs, 710 were trained and 290 untrained working at the PMTCT of HIV services in health facilities of the ten regions of Cameroon. A Multiple Choice Questionnaire (MCQ) on HIV management with focus on PMTCT of HIV was used to assess retention of HCWs at the health facility and retention of knowledge. Summary statistics described mean scores for retention of HCWs and retention of knowledge. One-way Analysis of Variance summarized the differences in retention of knowledge over time after training. Correlates for retention of knowledge were investigated by logistic regression analysis. Results: The retention of HCWs at health facilities in PMTCT of HIV services was 85%. Trained HCWs had higher mean scores for retention of knowledge than untrained HCWs, p < 0.001. Knowledge attrition was observed from 18, 24 to 36 months following training. Differences in the mean scores for retention of knowledge were observed between state-owned with private and confessionary health facilities but not among trained HCWs at 18, 24 or 36 months. Highest mean scores for retention of knowledge were observed in District Hospitals, Sub-Divisional Hospitals, and Integrated Health Centres. Correlates for retention of knowledge were: gender, type of health facility, location, longevity at PMTCT services, trained others and had means to apply what was trained to do Conclusion: Retention of trained HCWs at health facilities was high, mean scores for retention of knowledge was average and knowledge attrition was observed over time. This research is critical to understand where interventions may be most effective.
The physical sequelae of perinatally acquired HIV in adolescents: a research proposal
(2019-01) Comley‑White, Nicolette; Potterton, Joanne; Ntsiea, Veronica
Objectives: As the global access of antiretrovirals for HIV-infected infants improves, so the body of perinatally HIV-infected adolescents (PHIVA) grows. The neurological and physical complications of HIV, both in children and in adults, are well established, however there is a paucity of data pertaining to PHIVA, a group of people who have had a lifetime exposure to the virus and to antiretrovirals. There has been a resounding call for further research in this area, as well as for the development of policies and programmes for this population. The aim of this study is to determine the physical sequelae in PHIVA and to propose a model of care for this population. Methods: Through interviews with PHIVA, the perceived physical challenges will be established. Thereafter a cohort study with age-matched participants will determine if PHIVA have any limitations in fatigue, endurance, motor func‑ tion and muscle strength, body mass index, peripheral neuropathy, level of disability and quality of life. Using these results, a model of care will be proposed through the nominal group technique with both PHIVA and clinicians work‑ ing in HIV and adolescence.
Ad libitum water consumption prevents exercise-associated hyponatremia and protects against dehydration in soldiers performing a 40-km route-march
(BioMed Central, 2019-01) Nolte, Heinrich W.; Nolte, Kim; Hew-Butler, Tamara
Background: It remains unclear if ad libitum water drinking, as a hydration strategy, prevents exercise-associated hyponatremia (EAH) during prolonged exercise. The aim of this study was to determine the incidence of EAH within the broader context of fluid regulation among soldiers performing a 40-km route-march ingesting water ad libitum. Methods: Twenty-eight healthy male soldiers participated in this observational trial. Pre- and post-exercise body mass, blood and urine samples were collected. Blood samples were assessed for serum sodium ([Na+]), glucose, creatinine, urea nitrogen (BUN), plasma osmolality, creatine kinase (CK), and plasma arginine vasopressin (AVP) concentrations. Plasma volume (PV) was calculated using hematocrit and hemoglobin. Urine samples were analyzed for osmolality and [Na+]. Water intake was assessed by weighing bottles before, during and after the march. The mean relative humidity was 55.7% (21.9–94.3%) and the mean dry bulb temperature was 27.1 °C (19.5 °C - 37.0 °C) during the exercise. Results: Twenty-five soldiers (72 ± 10 kg) (Mean ± SD) completed the march in 09:11 ± 00:43 (hr:min). Participants consumed 736 ± 259 ml/h of water and lost 2.8 ± 0.9 kg (4.0% ± 1.4%, P < 0.05) of body mass. Significant (pre-march vs. post-march; P < 0.05) decreases in serum [Na+] (141 mmol/L vs. 136 mmol/L), plasma osmolality (303 mOsmol/kg H2O vs. 298 mOsmol/kg H2O), and serum creatinine (111 μmol/L vs. 101 μmol/L) and urine [Na+] (168 mmol/L vs. 142 mmol/L), as well as significant increases in plasma AVP (2 pg/ml vs. 11 pg/ml), plasma CK (1423 U/L vs. 3894 U/L) and urine osmolality (1035 mOsmol/kg H2O vs. 1097 mOsmol/kg H2O) were found. The soldier (72 kg) with the lowest postexercise sodium level completed the march in 08:38. He drank 800 ml/h, lost 2% body mass, and demonstrated (prepost) increases in plasma osmolality (294–314 mOsmol/kg H2O), BUN (20–30 mg/dl), AVP (2–16 pg/ml) and PV (41%). His urine osmolality decreased from 1114 mOsmol/kg H2O to 1110 mOsmol/kg H2O. No participants finished the route-march with a serum [Na+] indicating hypernatremia (range, 134–143 mmol/L). Conclusions: Ad libitum drinking resulted in 4% body mass loss with a 2 mmol/L serum [Na+] reduction in conjunction with high urine osmolality (> 1000 mOsmol/kg H2O) and plasma AVP. No single hydration strategy likely prevents EAH, but hypernatremia (cellular dehydration) was not seen despite > 2% body mass losses and high urine osmolality.
Evaluation of automated malaria diagnosis using the Sysmex XN-30 analyser in a clinical setting
(BioMed Central, 2019-01) Pillay, Evashin; Bezuidenhout, Belinda C.; Coetzer, Thérèsa L.; Khodaiji, Shanaz; Litshie, Monwabisi
Background: Early and accurate diagnosis of malaria is a critical aspect of eforts to control the disease, and several diagnostic tools are available. Microscopic assessment of a peripheral blood smear enables direct visualization of parasites in infected red blood cells and is the clinical diagnostic gold standard. However, it is subjective and requires a high level of skill. Numerous indirect detection methods are in use, but are not ideal since surrogate markers of infection are measured. This study describes the frst clinical performance evaluation of the automated Sysmex XN-30 analyser, which utilizes fuorescence fow cytometry to directly detect and quantitate parasite-infected red blood cells. Results: Residual EDTA blood samples from suspected malaria cases referred for routine diagnosis were analysed on the XN-30. Parasitaemia was reported as a percentage, as well as absolute numbers of infected red blood cells, and scattergrams provided a visual image of the parasitized red blood cell clusters. The results reported by the XN-30 correlated with microscopy and the analyser demonstrated 100% sensitivity and specifcity. Measurements were reproducible and storage of samples at room temperature did not afect the parameters. Several Plasmodium species were detected, including Plasmodium falciparum, Plasmodium vivax and Plasmodium ovale. The XN-30 also identifed the transmissible gametocytes as a separate cluster on the scattergrams. Abnormal red blood cell indices (low haemoglobin and raised reticulocyte counts), haemoglobinopathies and thrombocytopenia did not interfere with the detection of parasites. The XN-30 also generated a concurrent full blood count for each sample. Conclusions: The novel technology of the Sysmex XN-30 provides a robust, rapid, automated and accurate platform for diagnosing malaria in a clinical setting. The objective enumeration of red blood cells infected with Plasmodium species makes it suitable for global use and allows monitoring of the parasite load once therapy has been initiated, thereby providing an early marker of drug resistance. The automated generation of a full blood count for each sample provides an opportunity for detecting unsuspected cases. Asymptomatic carriers can also be identifed, which will be useful in blood transfusion centres, and will enable treatment of these individuals to prevent the spread of the disease.
Exploring the sorting of patients in community health centres across Gauteng Province, South Africa
(BioMed Central, 2019-01) Stott, B. A.; Moosa, S.
Background: Primary health care worldwide faces large numbers of patients daily. Poor waiting times, low patient satisfaction and staff burnout are some problems facing such facilities. Limited research has been done on sorting patients in non-emergency settings in Africa. This research looked at community health centres (CHCs) in Gauteng Province, South Africa where queues appear to be poorly managed and patients waiting for hours. This study explores the views of clinicians in CHCs across Gauteng on sorting systems in the non-emergency ambulatory setting. Methods: The qualitative study design used one-to-one, in-depth interviews of purposively selected doctors. Interviews were conducted in English, with open-ended exploratory questions. Interviews were recorded, transcribed, anonymised and checked by interviewees later. Data collection and analysis stopped with information saturation. The co-author supervised and cross-checked the process. A thematic framework was developed by both authors, before final thematic coding of all transcripts was undertaken by the principal author. This analysis was based on the thematic framework approach. Results: Twelve primary health care (PHC) doctors with experience in patient sorting, from health districts across Gauteng, were interviewed. Two themes were identified, two major themes, namely Systems Implemented and Innovative Suggestions, and Factors Affecting Triage. Systems Implemented included those using vital signs, sorting by specialties, and using the Integrated Management of Childhood Illnesses approach. Systems Implemented also included doctor - nurse triage, first come first serve, eyeball triage and sorting based on main complaint. Innovative Suggestions, such as triage room treatment and investigations, telephone triage, longer clinic hours and a booking system emerged. There were three Factors Affecting Triage: Management Factor, including general management issues, equipment, documentation, infrastructure, protocol, and uniformity; and Staff Factor, including general staffing issues education and teamwork; and Patient Factor. Conclusion: Developing a functional triage protocol with innovative systems for Gauteng is important. Findings from this study can guide the development of a functional triage system in the primary health care non-emergency outpatient setting of Gauteng’s CHCs. The Emergency Triage, Assessment and Treatment (ETAT) tool, modified for adult and non-clinician use, could help this. However, addressing management, staff and patient factors must be integral.
Lipid levels, insulin resistance and cardiovascular risk over 96 weeks of antiretroviral therapy: a randomised controlled trial comparing low-dose stavudine and tenofovir
(BioMed Central, 2018-12) Vos, Alinda G.; Chersich, Matthew F.; Klipstein‑Grobusch, Kerstin; Zuithof, Peter; Moorhouse, Michelle A.; Lalla‑Edward, Samanta T.; Kambugu, Andrew; Kumarasamy, N.; Grobbee, Diederick E.; Barth, Roos E.; Venter, Willem D.
Background: HIV infection and antiretroviral treatment are associated with changes in lipid levels, insulin resistance and risk of cardiovascular disease (CVD). We investigated these changes in the first 96 weeks of treatment with lowdose stavudine or tenofovir regimens. Methods: This is a secondary analysis of a double blind, randomised controlled trial performed in South-Africa, Uganda and India comparing low-dose stavudine (20 mg twice daily) with tenofovir in combination with efavirenz and lamivudine in antiretroviral-naïve adults (n = 1067) (Clinicaltrials.gov, NCT02670772). Over 96 weeks, data were collected on fasting lipids, glucose and insulin. Insulin resistance was assessed with the HOMA-IR index and 10-year CVD risk with the Framingham risk score (FRS). A generalized linear mixed model was used to estimate trends over time. Results: Participants were on average 35.3 years old, 57.6% female and 91.8% Black African. All lipid levels increased following treatment initiation, with the sharpest increase in the first 24 weeks of treatment. The increase in all lipid subcomponents over 96 weeks was higher among those in the stavudine than the tenofovir group. Insulin resistance increased steadily with no difference detected between study groups. FRS rose from 1.90% (1.84–1.98%) at baseline to 2.06 (1.98–2.15%) at week 96 for the total group, with no difference between treatment arms (p = 0.144). Lipid changes were more marked in Indian than African participants. Conclusion: Lipid levels increased in both groups, with low-dose stavudine resulting in a worse lipid profile compared to tenofovir. Insulin resistance increased, with no difference between regimens. CVD risk increased over time and tended to increase more in the group on stavudine. The low CVD risk across both arms argues against routine lipid and glucose monitoring in the absence of other CVD risk factors. In high risk patients, monitoring may only be appropriate at least a year after treatment initiation.

1. Academic Wits Research Publications (Faculties submissions)

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