Intramural: Journal Articles

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All papers that are published (or in the process of being published) in a scientific journal by SAMRC staff.


Recent Submissions

  • Publication
    Medical Encounters in a 90-km Ultramarathon Running Event: A 6-year Study in 103 131 Race Starters—SAFER XVII
    (Wolters Kluwer, 2022-01-01) Sewry, N.; Schwellnus, M.; Boulter, J.; Seocharan, I.; Jordaan, E.; Biostatistics Unit, South African Medical Research Council, South Africa.
    Objective: To determine the incidence and nature of illness-related medical encounters (MEs) at a 90-km, ultramarathon, mass, community-based, endurance running event. Design: Retrospective, descriptive epidemiological study. Setting: Comrades Marathon (90 km), South Africa. Participants: One lakh three thousand one hundred thirty-one race starters over 6 years (2014-2019). Independent variables: Incidence of moderate and serious/life-threatening MEs. Main outcome measures: All MEs were recorded by race medical doctors on race day each year. Medical encounters were recorded by severity, organ system, and final specific diagnosis (2019 consensus statement definition on mass community-based events). Incidences (I: per 1000 starters; 95% confidence intervals) were calculated for MEs. Results: There were 1971 illness-related MEs, with an overall incidence of 19.1 (range, 18.3-20.0). The incidence for serious/life-threatening MEs was 1.8 (range, 1.6-2.1). Incidences of MEs by organ systems affected were as follows: fluid/electrolyte (8.8; 8.3-9.4), central nervous system (4.0; 3.7-4.5), and gastrointestinal system (2.9; 2.6-3.2). Dehydration (I = 7.5: 7.0-8.1) and exercise-associated muscle cramping (I = 3.2: 2.9-3.6) were the 2 most common specific diagnoses. Conclusion: The incidence of MEs in the 90-km Comrades Marathon was one of the highest incidences of MEs reported in an endurance running event (1 in 52 starters and 1 in 556 starters for serious/life-threatening MEs). Preventative measures to reduce MEs are needed, and further investigations into the risk factors associated with MEs could assist in managing the risk and better prepare athletes, race organizers, and medical directors.
  • Publication
    Identification of potential biomarkers for predicting the early onset of diabetic cardiomyopathy in a mouse model
    (Nature Publishing Group, 2020-07-23) Johnson, R.; Nxele, X.; Cour, M.; Sangweni, N.; Jooste, T.; Hadebe, N.; Samodien, E.; Benjeddou, M.; Mazino, M.; Louw, J.; Lecour, S.; Rabia Johnson: Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council
    Type 2 diabetes (T2D) is characterized by metabolic derangements that cause a shift in substrate preference, inducing cardiac interstitial fibrosis. Interstitial fibrosis plays a key role in aggravating left ventricular diastolic dysfunction (LVDD), which has previously been associated with the asymptomatic onset of heart failure. The latter is responsible for 80% of deaths among diabetic patients and has been termed diabetic cardiomyopathy (DCM). Through in silico prediction and subsequent detection in a leptin receptor-deficient db/db mice model (db/db), we confirmed the presence of previously identified potential biomarkers to detect the early onset of DCM. Differential expression of Lysyl Oxidase Like 2 (LOXL2) and Electron Transfer Flavoprotein Beta Subunit (ETFβ), in both serum and heart tissue of 6-16-week-old db/db mice, correlated with a reduced left-ventricular diastolic dysfunction as assessed by high-resolution Doppler echocardiography. Principal component analysis of the combined biomarkers, LOXL2 and ETFβ, further displayed a significant difference between wild type and db/db mice from as early as 9 weeks of age. Knockdown in H9c2 cells, utilising siRNA of either LOXL2 or ETFβ, revealed a decrease in the expression of Collagen Type I Alpha1 (COL1A1), a marker known to contribute to enhanced myocardial fibrosis. Additionally, receiver-operating curve (ROC) analysis of the proposed diagnostic profile showed that the combination of LOXL2 and ETFβ resulted in an area under the curve (AUC) of 0.813, with a cut-off point of 0.824, thus suggesting the favorable positive predictive power of the model and further supporting the use of LOXL2 and ETFβ as possible early predictive DCM biomarkers.
  • Publication
    Health worker experiences of and perspectives on engaging men in HIV care: A qualitative study in Cape Town, South Africa
    (SAGE, 2020-05-29) Mbokazi, N.; Madzima, R.; Leon, N.; Lurie, M.N.; Cornell, M.; Schmidt, B.M.; Colvin, C.J.; Health Systems Research Unit & Cocrane South Africa, South African Medical Research Council
    Men generally fare worse than women across the HIV cascade. While we know much about how men perceive the health services, we know little about how health workers (HWs) themselves have experienced engaging with men and what strategies they have used to improve this engagement. We interviewed 12 HWs in public health care services in Cape Town to better understand their experiences and perspectives. Health workers felt there were significant gaps in men's engagement with HIV care and identified masculine gender norms, the persistent impact of HIV stigma, and the competing priorities of employment as key barriers. They also highlighted a number of health service-related challenges, including a poor perception of the patient-provider relationship, frustration at low service quality, and unrealistic expectations of the health services. Health workers also described several strategies for more effectively engaging men and for making the health services both more male friendly and more people friendly.
  • Publication
    The effectiveness of peer and community health worker-led self-management support programs for improving diabetes health-related outcomes in adults in low-and-middle-income countries: A systematic review
    (BMC, 2020-06-06) Werfalli, M.; Raubenheimer, P.J.; Engel, M.; Musekiwa, A.; Bobrow, K.; Peer, N.; Hoegfeldt, C.; Kalula, S.; Kengne, A.P.; Levitt, N.S.; South African Medical Research Council
    Objective: Community-based peer and community health worker-led diabetes self-management programs (COMP-DSMP) can benefit diabetes care, but the supporting evidence has been inadequately assessed. This systematic review explores the nature of COMP-DSMP in low- and middle-income countries' (LMIC) primary care settings and evaluates implementation strategies and diabetes-related health outcomes. Methods: We searched the Cochrane Library, PubMed-MEDLINE, SCOPUS, CINAHL PsycINFO Database, International Clinical Trials Registry Platform,, Pan African Clinical Trials Registry (PACTR), and HINARI (Health InterNetwork Access to Research Initiative) for studies that evaluated a COMP-DSMP in adults with either type 1 or type 2 diabetes in World Bank-defined LMIC from January 2000 to December 2019. Randomised and non-randomised controlled trials with at least 3 months follow-up and reporting on a behavioural, a primary psychological, and/or a clinical outcome were included. Implementation strategies were analysed using the standardised implementation framework by Proctor et al. Heterogeneity in study designs, outcomes, the scale of measurements, and measurement times precluded meta-analysis; thus, a narrative description of studies is provided. Results: Of the 702 records identified, eleven studies with 6090 participants were included. COMP-DSMPs were inconsistently associated with improvements in clinical, behavioural, and psychological outcomes. Many of the included studies were evaluated as being of low quality, most had a substantial risk of bias, and there was a significant heterogeneity of the intervention characteristics (for example, peer definition, selection, recruitment, training and type, dose, and duration of delivered intervention), such that generalisation was not possible. Conclusions: The level of evidence of this systematic review was considered low according to the GRADE criteria. The existing evidence however does show some improvements in outcomes. We recommend ongoing, but well-designed studies using a framework such as the MRC framework for the development and evaluation of complex interventions to inform the evidence base on the contribution of COMP-DSMP in LMIC.
  • Publication
    Unspoken inequality: How COVID-19 has exacerbated existing vulnerabilities of asylum-seekers, refugees, and undocumented migrants in South Africa
    (BMC, 2020-08-20) Mukumbang, F.C.; Ambe, A.N.; Adebiyi, B.O.; Burden of Disease Research Unit, South African Medical Research Council
    An estimated 2 million foreign-born migrants of working age (15-64) were living in South Africa (SA) in 2017. Structural and practical xenophobia has driven asylum-seekers, refugees, and undocumented migrants in SA to abject poverty and misery. The Coronavirus Disease 2019 (COVID-19) containment measures adopted by the SA government through the lockdown of the nation have tremendously deepened the unequal treatment of asylum-seekers and refugees in SA. This can be seen through the South African government's lack of consideration of this marginalized population in economic, poverty, and hunger alleviation schemes. Leaving this category of our society out of the national response safety nets may lead to negative coping strategies causing mental health issues and secondary health concerns. An effective response to the socioeconomic challenges imposed by the COVID-19 pandemic should consider the economic and health impact of the pandemic on asylum-seekers, refugees, and undocumented migrants.
  • Publication
    Linking LOXL2 to cardiac interstitial fibrosis
    (MDPI, 2020-08-18) Erasmus, M.; Samodien, E.; Lecour, S.; Cour, M.; Lorenzo, O.; Dludla, P.; Pheiffer, C.; Johnson, R.; Biomedical Research and Innovation Platform, South African Medical Research Council
    Cardiovascular diseases (CVDs) are the leading causes of death worldwide. CVD pathophysiology is often characterized by increased stiffening of the heart muscle due to fibrosis, thus resulting in diminished cardiac function. Fibrosis can be caused by increased oxidative stress and inflammation, which is strongly linked to lifestyle and environmental factors such as diet, smoking, hyperglycemia, and hypertension. These factors can affect gene expression through epigenetic modifications. Lysyl oxidase like 2 (LOXL2) is responsible for collagen and elastin cross-linking in the heart, and its dysregulation has been pathologically associated with increased fibrosis. Additionally, studies have shown that, LOXL2 expression can be regulated by DNA methylation and histone modification. However, there is a paucity of data on LOXL2 regulation and its role in CVD. As such, this review aims to gain insight into the mechanisms by which LOXL2 is regulated in physiological conditions, as well as determine the downstream effectors responsible for CVD development.
  • Publication
    Role of vaccines in preventing influenza in healthy children
    (HMPG, 2021-03-02) Sambala, E.Z.; Cooper, S.; Schmidt, B.M.; Walaza, S.; Wiysonge, C.S.; Cochrane South Africa, South African Medical Research Council, Cape Town, South Africa.
    The role of an influenza vaccine is to minimise illness and death. Vaccines provide good protection against influenza strains and significantly reduce time off work. However, the recommendation for use depends on the efficacy, effectiveness and safety of the vaccines. We highlight a Cochrane review that sought to determine the efficacy, effectiveness and safety of seasonal influenza vaccines in healthy children, and provide implications for practice for vaccination of children. The findings suggest that influenza vaccines play a key role in reducing serious morbidity and mortality among children. There were few data available to provide firm conclusions on adverse events. Vaccinating against influenza not only reduces its incidence among children, but also extends these benefits to the unvaccinated population, such as the elderly. In light of the many direct and indirect benefits of vaccinating children aged 2 - 16 years, there is a need to provide access to influenza vaccines to all eligible South African children.
  • Publication
    Inter-Comparison Campaign of Solar UVR Instruments under Clear Sky Conditions at Reunion Island (21◦S, 55◦E)
    (MDPI, 2020-04-19) Cadet, J. M.; Portafaix, T; Bencherif, H; Lamy, K; Brogniez, C; Auriol, F; Metzger, J.M; Boudreault, L.E.; Wright, C.Y.; Environment and Health Research Unit, South African Medical Research Council
    Measurement of solar ultraviolet radiation (UVR) is important for the assessment of potential beneficial and adverse impacts on the biosphere, plants, animals, and humans. Excess solar UVR exposure in humans is associated with skin carcinogenesis and immunosuppression. Several factors influence solar UVR at the Earth's surface, such as latitude and cloud cover. Given the potential risks from solar UVR there is a need to measure solar UVR at different locations using effective instrumentation. Various instruments are available to measure solar UVR, but some are expensive and others are not portable, both restrictive variables for exposure assessments. Here, we compared solar UVR sensors commercialized at low or moderate cost to assess their performance and quality of measurements against a high-grade Bentham spectrometer. The inter-comparison campaign took place between March 2018 and February 2019 at Saint-Denis, La Réunion. Instruments evaluated included a Kipp&Zonen UVS-E-T radiometer, a Solar Light UV-Biometer, a SGLux UV-Cosine radiometer, and a Davis radiometer. Cloud fraction was considered using a SkyCamVision all-sky camera and the Tropospheric Ultraviolet Visible radiative transfer model was used to model clear-sky conditions. Overall, there was good reliability between the instruments over time, except for the Davis radiometer, which showed dependence on solar zenith angle. The Solar Light UV-Biometer and the Kipp&Zonen radiometer gave satisfactory results, while the low-cost SGLux radiometer performed better in clear sky conditions. Future studies should investigate temporal drift and stability over time.
  • Publication
    Association of deworming with reduced eosinophilia: implications of HIV/AIDS and co-endemic diseases
    (2003) Schoeman S.E.; Markus M.B.; Bentwich Z.; Mansvelt E.P.G.; Adams V.J.; Fincham J.E.; Dhansay M.A.; Lombard, C.J.; Medical Research Council, P O Box 19070, South Africa
    Eosinophil counts in venous blood were monitored during a randomized controlled deworming trial (n = 155 children) that lasted for a year, and in a whole-school deworming programme (range 174-256 children) of 2 years' duration. Mean eosinophil counts (×109 / l) decreased from 0.70 in the randomized trial, and 0.61 in the whole-school study, to well within the normal paediatric range of 0.05-0.45 (P < 0.05). The prevalence of eosinophilia declined from 57% to 37% in the randomized trial (mean for 400, 800 and 1200 mg albendazole doses); and from 47% to 24% in the whole-school study (500 mg stat mebendazole). Benzimidazole anthelminthics were highly effective against Ascaris but less so against Trichuris. Activated eosinophils are effector and immunoregulatory leucocytes of the T-helper cell type 2 (Th2) immune response to parasitic helminths and atopic disorders. Under conditions of poverty where soil-transmitted helminths are hyperendemic, Th2 polarization of the immune profile is characteristic. Regular anthelminthic treatment should reduce contact with worm antigens, and this may contribute to re-balancing of the immune profile. Suppression of eosinophil recruitment and activation, together with related cellular and molecular immunological changes, might have positive implications for prevention and treatment of co-endemic diseases, including HIV / AIDS, cholera, tuberculosis and atopic disorders..
  • Publication
    Fumonisin mycotoxins in human hair
    (2003) Sewram, V.; Mshicilelo, N.; Shephard, G.S.; Marasas, W.F.O; Promec Unit, Medical Research Council, PO Box 19070, Tygerberg, 7505, South Africa.
    This study shows for the first time the accumulation of fumonisin mycotoxins in human hair of population clusters exposed to contaminated maize, and thus the feasibility of human hair analysis for the assessment of past fumonisin exposure. Composite hair samples were obtained from the Bizana, Butterworth and Centane districts within the Transkei region of the Eastern Cape Province of South Africa. Following methanol extraction and strong anion exchange clean up, the fumonisins FB1, FB2 and FB3 were detected using high performance liquid chromatography coupled to electrospray ionization-mass spectrometry (HPLC-ESI-MS). Hair from Centane and Butterworth showed mean levels of FB1 of 26.7 and 23.5 μg kg-1 hair, respectively. FB2 was only detected in hair from Centane and in one sampling point in Butterworth, with mean levels of 6.5 and 5.7 μg kg-1 hair, respectively. Hair samples from Bizana, on the other hand, were found to contain higher levels of FB1 (mean 33.0 μg kg-1 hair) and FB2 (mean 11.1 μg kg-1 hair). No samples contained more than trace levels of FB3. Recoveries from spiked hair samples using this method ranged from 81% to 101%, demonstrating the applicability of hair analysis in assessing human exposure to fumonisin mycotoxins..
  • Publication
    Influence of the G2 cell cycle block abrogator pentoxifylline on the expression and subcellular location of cyclin B1 and p34(cdc2) in HeLa cervical carcinoma cells
    (1999) Theron, T.; Böhm, L.
    Abstract. The progression of cells from G2 into mitosis in mainly controlled by formation of the cyclin B1/p34cdc2 complex. The behavior of this complex in the irradiation-induced G2 cell cycle delay is still unclear. A prior study demonstrated that the expression of the cyclin B1 protein is reduces by irradiation, and restored to control levels by the methyl xanthine drug pentoxifylline, which is a potent G2 block abrogator. The present study shows that irradiation, and 2 mM pentoxifylline affect the expression of the cyclin-dependent kinase p34cdc2 in HeLa cells. Irradiation induced p34cdc2 levels to increase and cyclin B1 levels to decrease. Addition of pentoxifylline at the G2 maximum reverses these trends. This is also evident from the cyclin B1/34cdc2 ratios which decline after irradiation and are rapidly restored to control levels upon addition of pentoxifylline. It is concluded that cyclin B1 and p34cdc2 protein expression are important events and act in concert to control the irradiation induced G2 block. Analysis of cyclin B1 expression in whole cells and in isolated nuclei furthermore show that cyclin B1 translocated from the nucleus into the cytoplasm when the G2 block is abrogated by pentoxifylline.
  • Publication
    The MRC/Wits dental research Institute: its publication record 1954-2004.
    (Academy of Science for South Africa, 2006) Grossman, E.S.; Mogotsi, M.; Cleaton-Jones, P.E.; Dental Research Institute, University of the Witwatersrand, Private Bag 3, WITS 2050, South Africa. †Author for correspondence. E-mail:
    All 625 scientific papers published by the Dental Research Institute (DRI) during its life between 1954 and 2004 were examined and categorized according to publishing journal, article content and author, with the aim of obtaining information on research collaboration, quality, productivity and author representivity. Currently, 11% of authors are from disadvantaged backgrounds and 32% are women. Collaborators make up half of co-authors and presently are South African academics (31%) or from the associated dental school (19%). In the period 1985-1994, 28% of collaborators were from abroad. Research quality as assessed by journal impact factor, experimental method, research design and ethical protocols shows improving scientific rigour, adherence to international scientific standards and publication in well-regarded journals. This analysis provides a unique opportunity to assess research output against the challenging and changing backdrop of the local and global dental research environment. In addition, this is the first detailed record of a South African research entity which jointly reflects both university and statutory body research trends over 50 years. In this alone, the DRI database provides a unique historical record that shows how the institute has been transformating for the past half-century.
  • Publication
    Interleukin‐6 Inhibitor, Tocolizumab, for COVID‐19: evidence review of the clinical  benefit and harm
    (South African National Department of Health, 2020-04-15) Parrish, A.; Gray, A. ; Kredo, T. ; Maartens, G. ; Reubenson, G.; Cohen, K.; De Waal, R.; Blockman, M.; Nel, J.; Rees, H.;  Cochrane South Africa, South  African Medical Research Council
  • Publication
    Lopinavir–ritonavir (LPV/r) for treatment of COVID‐19: evidence review of clinical benefits and harms
    (South African National Department of Health, 2020-04-22) Parrish, A.; Gray, A.; Kredo, T.; Maartens, G. ; Reubenson, G.; Cohen, K. ; De Waal, R.; Blockman, M.; Nel, J.; Rees, H.; Tamara Kredo: Cochrane South Africa, South African Medical Research Council)
  • Publication
    Azithromycin for COVID‐19: evidence review of the clinical benefit and harm
    (South African National Department of Health , 2020-05-11) Blockman, M.; Cohen, K.; De Waal, R. ; Gray, A.; Kredo, T. ; Maartens, G. ; Nel, J.; Parrish, A.; Rees, H.; Reubenson, G.; (Cochrane South Africa, South  African Medical Research Council, SA GRADE Network)
  • Publication
    Favipiravir for the prevention and management of COVID‐19: evidence review of the clinical benefit and harm
    (South African National Department of Health, 2020-06-25) Blockman, M.; Cohen, K. ; De Waal, R.; Gray, A.; Kredo, T.; Maartens, G.; Nel, J.; Parrish, A.; Rees, H.; Reubenson, G.; Cochrane South Africa, South  African Medical Research Council
  • Publication
    Corticosteroids for COVID‐19: evidence review of the ckinical benefit and harm
    (South African National Department of Health, 2020-07-23) Blockman, M.; Cohen, K.; De Waal, R.; Gray, A. ; Kredo, T.; Maartens, G.; Nel, J. ; Parrish, A.; Rees, H. ; Reubenson, G.; SD and TK (Cochrane South Africa, South  African Medical Research Council, SA GRADE Network)
  • Publication
     Remdesivir for COVID‐19: evidence review of the clinical benefit and harm
    (South African National Department of Health , 2020-06-24) Blockman, M.; Cohen, K.; De Waal, R.; Gray, A.; Kredo, T.; Maartens, G.; Nel, J.; Parrish, A.; Rees, H.; Reubenson, G.; SD and TK (Cochrane South Africa, South  African Medical Research Council, SA GRADE Network)
  • Publication
    Chloroquine and hydroxychloroquine for prevention of COVID‐19: evidence review of clinical benefits and harm
    (South African National Department of Health, 2020-06-18) Blockman, M.; Cohen, K.; De Waal, R.; Gray, A.; Kredo, T.; Maartens, G.; Nel, J.; Parrish, A.; Rees, H.; SD and TK (Cochrane South Africa, South  African Medical Research Council, SA GRADE Network), MB (Division of Clinical Pharmacology, Department of Medicine,  Groote Schuur Hospital, University of Cape Town)
  • Publication
    Continuing Low Colon Cancer Incidence in African Populations
    (Elsevier, 2000) Segal, I.; Edwards, C.A.; Walker, A.R.; South Africa institute for Medical Research Johannesburg, South Africa