Faculty of Medicine and Health Sciences

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The vision of the Faculty of Medicine and Health Sciences is to be a dynamic, people-centred and inclusive environment, internationally recognised for its excellence in research, education and clinical training in medicine and health sciences, and for the contribution it makes to improving health and health care in South Africa, the African continent and beyond.

This faculty was known as the Faculty of Health Sciences until 30 April 2012.

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A 10-year review of fatal community assault cases at a regional forensic pathology facility in Cape Town, South Africa
(Health and Medical Publishing Group, 2015) Herbst, Celeste Ingrid; Tiemensma, Marianne; Wadee, Shabir Ahmed
Background. An increase in autopsied community assault (CA) fatalities was observed at the Tygerberg Forensic Pathology Services (FPS), Cape Town, South Africa (SA). There is a paucity of information on the incidence and prevalence of these cases in SA. Objectives. To determine the patterns and trends of injuries sustained in so-called CA fatalities. Methods. A retrospective and descriptive study was conducted. Fatal CA cases admitted to the Tygerberg FPS over the 10-year period 1 January 2003 - 31 December 2012 were reviewed. Data were collected from autopsy/postmortem reports, contemporaneous notes, attached hospital records, the South African Police Services (SAPS) 180 form (completed by the SAPS representative) and other FPS documentation. Results. A total of 424 cases of fatal CA were seen during the study period, with an annual increase between 2003 and 2007 and a second peak in 2012. The cause of death in most cases was multiple injuries (42.0%), with blunt-force trauma being the basis of most injuries sustained. The area with the greatest burden of injury was the township of Mfuleni (73 CA deaths per 100 000 population). There was a predominance of males, with only one female fatality recorded. Conclusion. Adequate policing in prevalent areas is essential to address unnecessary loss of life and the burden imposed by these cases on the criminal justice system and healthcare services.
1000 Genomes-based metaanalysis identifies 10 novel loci for kidney function
(Nature Research, 2017) Gorski, Mathias; Van Der Most, Peter J.; Teumer, Alexander; Chu, Audrey Y.; Li, Man; Mijatovic, Vladan; Nolte, Ilja M.; Cocca, Massimiliano; Taliun, Daniel; Gomez, Felicia; Li, Yong; Tayo, Bamidele; Tin, Adrienne; Feitosa, Mary F.; Aspelund, Thor; Attia, John; Biffar, Reiner; Bochud, Murielle; Boerwinkle, Eric; Borecki, Ingrid; Bottinger, Erwin P.; Chen, Ming-Huei; Chouraki, Vincent; Ciullo, Marina; Coresh, Josef; Cornelis, Marilyn C.; Curhan, Gary C.; d’Adamo, Adamo Pio; Dehghan, Abbas; Dengler, Laura; Ding, Jingzhong; Eiriksdottir, Gudny; Endlich, Karlhans; Enroth, Stefan; Esko, Tonu; Franco, Oscar H.; Gasparini, Paolo; Gieger, Christian; Girotto, Giorgia; Gottesman, Omri; Gudnason, Vilmundur; Gyllensten, Ulf; Hancock, Stephen J.; Harris, Tamara B.; Helmer, Catherine; Hollerer, Simon; Hofer, Edith; Hofman, Albert; Holliday, Elizabeth G.; Homuth, Georg; Hu, Frank B.; Huth, Cornelia; Hutri-Kahonen, Nina; Hwang, Shih-Jen; Imboden, Medea; Johansson, Asa; Kahonen, Mika; Konig, Wolfgang; Kramer, Holly; Kramer, Bernhard K.; Kumar, Ashish; Kutalik, Zoltan; Lambert, Jean-Charles; Launer, Lenore J.; Lehtimaki, Terho; De Borst, Martin H.; Navis, Gerjan; Swertz, Morris; Liu, Yongmei; Lohman, Kurt; Loos, Ruth J. F.; Lu, Yingchang; Lyytikainen, Leo-Pekka; McEvoy, Mark A.; Meisinger, Christa; Meitinger, Thomas; Metspalu, Andres; Metzger, Marie; Mihailov, Evelin; Mitchell, Paul; Nauck, Matthias; Oldehinkel, Albertine J.; Olden, Matthias; Penninx, Brenda W. J. H.; Pistis, Giorgio; Pramstaller, Peter P.; Probst-Hensch, Nicole; Raitakari, Olli T.; Rettig, Rainer; Ridker, Paul M.; Rivadeneira, Fernando; Robino, Antonietta; Rosas, Sylvia E.; Ruderfer, Douglas; Ruggiero, Daniela; Saba, Yasaman; Sala, Cinzia; Schmidt, Helena; Schmidt, Reinhold; Scott, Rodney J.; Sedaghat, Sanaz; Smith, Albert V.; Sorice, Rossella; Stengel, Benedicte; Stracke, Sylvia; Strauch, Konstantin; Toniolo, Daniela; Uitterlinden, Andre G.; Ulivi, Sheila; Viikari, Jorma S.; Volker, Uwe; Vollenweider, Peter; Volzke, Henry; Vuckovic, Dragana; Waldenberger, Melanie; Wang, Jie Jin; Yang, Qiong; Chasman, Daniel I.; Tromp, Gerard; Snieder, Harold; Heid, Iris M.; Fox, Caroline S.; Kottgen, Anna; Pattaro, Cristian; Boger, Carsten A.; Fuchsberger, Christian
HapMap imputed genome-wide association studies (GWAS) have revealed >50 loci at which common variants with minor allele frequency >5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-analysis of kidney function based on the estimated glomerular filtration rate (eGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value < 5 × 10−8 previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique to the 1000 Genomes reference panel. Using pathway analysis, we identified 39 significant (FDR < 0.05) genes and 127 significantly (FDR < 0.05) enriched gene sets, which were missed by our previous analyses. Among those, the 10 identified novel genes are part of pathways of kidney development, carbohydrate metabolism, cardiac septum development and glucose metabolism. These results highlight the utility of re-imputing from denser reference panels, until whole-genome sequencing becomes feasible in large samples.
10Kin1day : a bottom-up neuroimaging initiative
(Frontiers Media, 2019) Van den Heuvel, Martijn P.; Scholtens, Lianne H.; Van der Burgh, Hannelore K.; Agosta, Federica; Alloza, Clara; Arango, Celso; Auyeung, Bonnie; Baron-Cohen, Simon; Basaia, Silvia; Benders, Manon J. N. L.; Beyer, Frauke; Booij, Linda; Braun, Kees P. J.; Filho, Geraldo Busatto; Cahn, Wiepke; Cannon, Dara M.; Chaim-Avancini, Tiffany M.; Chan, Sandra S. M.; Chen, Eric Y. H.; Crespo-Facorro, Benedicto; Crone, Eveline A.; Dannlowski, Udo; De Zwarte, Sonja M. C.; Dietsche, Bruno; Donohoe, Gary; Du Plessis, Stefan; Durston, Sarah; Diaz-Caneja, Covadonga M.; Díaz-Zuluaga, Ana M.; Emsley, Robin; Filippi, Massimo; Frodl, Thomas; Gorges, Martin; Graff, Beata; Grotegerd, Dominik; Gąsecki, Dariusz; Hall, Julie M.; Holleran, Laurena; Holt, Rosemary; Hopman, Helene J.; Jansen, Andreas; Janssen, Joost; Jodzio, Krzysztof; Jancke, Lutz; Kaleda, Vasiliy G.; Kassubek, Jan; Masouleh, Shahrzad Kharabian; Kircher, Tilo; Koevoets, Martijn G. J. C.; Kostic, Vladimir S.; Krug, Axel; Lawrie, Stephen M.; Lebedeva, Irina S.; Lee, Edwin H. M.; Lett, Tristram A.; Lewis, Simon J. G.; Liem, Franziskus; Lombardo, Michael V.; Lopez-Jaramillo, Carlos; Margulies, Daniel S.; Markett, Sebastian; Marques, Paulo; Martinez-Zalacaín, Ignacio; McDonald, Colm; McIntosh, Andrew M.; McPhilemy, Genevieve; Meinert, Susanne L.; Menchon, Jose M.; Montag, Christian; Moreira, Pedro S.; Morgado, Pedro; Mothersill, David O.; Merillat, Susan; Muller, Hans-Peter; Nabulsi, Leila; Najt, Pablo; Narkiewicz, Krzysztof; Naumczyk, Patrycja; Oranje, Bob; De la Foz, Victor Ortiz-Garcia; Peper, Jiska S.; Pineda, Julian A.; Rasser, Paul E.; Redlich, Ronny; Repple, Jonathan; Reuter, Martin; Rosa, Pedro G. P.; Ruigrok, Amber N. V.; Sabisz, Agnieszka; Schall, Ulrich; Seedat, Soraya, 1966-; Serpa, Mauricio H.; Skouras, Stavros; Soriano-Mas, Carles; Sousa, Nuno; Szurowska, Edyta; Tomyshev, Alexander S.; Tordesillas-Gutierrez, Diana; Valk, Sofie L.; Van den Berg, Leonard H.; Van Erp, Theo G. M.; Van Haren, Neeltje E. M.; Van Leeuwen, Judith M. C.; Villringer, Arno; Vinkers, Christiaan H.; Vollmar, Christian; Waller, Lea; Walter, Henrik; Villringer, Arno; Vinkers, Christiaan H.; Vollmar, Christian; Waller, Lea; Walter, Henrik; Whalley, Heather C.; Witkowska, Marta; Witte, A. Veronica; Zanetti, Marcus V.; Zhang, Rui; De Lange, Siemon C.
Parkinson’s disease (PD) is a well-known neurodegenerative disease with a strong association established with systemic inflammation. Recently, the role of the gingipain protease group from Porphyromonas gingivalis was implicated in Alzheimer’s disease and here we present evidence, using a fluorescent antibody to detect gingipain R1 (RgpA), of its presence in a PD population. To further elucidate the action of this gingipain, as well as the action of the lipopolysaccharide (LPS) from P. gingivalis, low concentrations of recombinant RgpA and LPS were added to purified fluorescent fibrinogen. We also substantiate previous findings regarding PD by emphasizing the presence of systemic inflammation via multiplex cytokine analysis, and demonstrate hypercoagulation using thromboelastography (TEG), confocal and electron microscopy. Biomarker analysis confirmed significantly increased levels of circulating proinflammatory cytokines. In our PD and control blood analysis, our results show increased hypercoagulation, the presence of amyloid formation in plasma, and profound ultrastructural changes to platelets. Our laboratory analysis of purified fibrinogen with added RgpA, and/or LPS, showed preliminary data with regards to the actions of the protease and the bacterial membrane inflammagen on plasma proteins, to better understand the nature of established PD.
The 12-month period prevalence and cardiac manifestations of HIV in patients with acute coronary syndrome at a tertiary hospital in Cape Town, South Africa : a retrospective cross-sectional study
(BMC (part of Springer Nature), 2021) Pennefather, Camilla; Esterhuizen, Tonya; Doubell, Anton; Decloedt, Eric H.
Background: HIV-positive patients are increasingly being affected by non-communicable diseases such as coronary artery disease (CAD). Data from high-income countries (HICs) indicate that HIV-positive patients have different riskfactor profiles for acute coronary syndrome (ACS) as well as different cardiac manifestations of this syndrome compared to HIV-negative patients. There is limited data from Sub-Saharan Africa (SSA), and particularly from South Africa with the biggest HIV epidemic in the world. The objective of this study was to determine the 12-month period prevalence of HIV in patients with ACS and to compare the risk-factor profile, ACS presentation and management between HIV-positive and HIV-negative adults. Methods: We included all patients hospitalised with ACS from 01 January to 31 December 2018 in a tertiary hospital, Tygerberg Hospital, in Cape Town, South Africa. The HIV-status of all patients was determined using routine clinical records. We performed multiple conditional logistic regression on HIV-positive and HIV-negative patients (1:3 ratio) to compare the risk factor profile, ACS presentation and management between the groups. Results: Among 889 patients, 30 (3.4%) were HIV-positive (95% confidence interval (CI): 2.3–4.8). HIV-positive patients were younger, more frequently men, and had a lower prevalence of medical comorbidities and a family history of CAD. They were more likely to present with ST-elevation myocardial infarction (STEMI) [odd’s ratio (OR) (95% CI): 3.12 (1.2–8.4)], and have single-vessel disease [OR (95% CI): 3.03 (1.2–8.0)]. Angiographic and echocardiographic data, as well as management, did not differ between the groups. Among HIV-positive patients, 17 (65%) were virally suppressed (HIV viral load < 200 copies/mL) with a median CD4+ count of 271 cells/mm3. The majority (20, 67%) of HIV-positive patients were receiving antiretroviral therapy at the time of the ACS. Conclusions: We found an HIV-prevalence of 3.4% (95% CI 2.3–4.8) in adults with ACS in a high endemic HIV region. HIV-positive patients were younger and more likely to present with STEMIs and single-vessel disease, but had fewer CAD risk factors, suggesting additional mechanisms for the development of ACS.
The 17th International Congress on Infectious Diseases workshop on developing infection prevention and control resources for low - and middle-income countries
(Published by Elsevier on behalf of International Society for Infectious Diseases, 2017) Sastry, Sangeeta; Masroor, Nadia; Bearman, Gonzalo; Hajjeh, Rana; Holmes, Alison; Memish, Ziad; Lassmann, Britta; Pittet, Didier; Macnab, Fiona; Kamau, Rachel; Wesangula, Evelyn; Pokhare, Paras; Brown, Paul; Daily, Frances; Amer, Fatma; Torres, Jaime; O’Ryan, Miguel; Gunturu, Revathi; Bulabula, Andre; Mehtarp, Shaheen
Hospital-acquired infections (HAIs) are a major concern to healthcare systems around the world. They are associated with significant morbidity and mortality, in addition to increased hospitalization costs. Recent outbreaks, including those caused by the Middle East respiratory syndrome coronavirus and Ebola virus, have highlighted the importance of infection control. Moreover, HAIs, especially those caused by multidrug-resistant Gram-negative rods, have become a top global priority. Although adequate approaches and guidelines have been in existence for many years and have often proven effective in some countries, the implementation of such approaches in low- and middle-income countries (LMICs) is often restricted due to limited resources and underdeveloped infrastructure. While evidence-based infection prevention and control (IPC) principles and practices are universal, studies are needed to evaluate simplified approaches that can be better adapted to LMIC needs, in order to guide IPC in practice. A group of experts from around the world attended a workshop held at the 17th International Congress on Infectious Diseases in Hyderabad, India in March 2016, to discuss the existing IPC practices in LMICs, and how best these can be improved within the local context.
2'-5'-Oligoadenylate synthetase-like protein inhibits intracellular M. tuberculosis replication and promotes proinflammatory cytokine secretion
(Elsevier, 2019-12) Leisching, G.; Ali, A.; Cole, V.; Baker, B.
Host cytoplasmic surveillance pathways are known to elicit type I interferon (IFN) responses which are crucial to antimicrobial defense mechanisms. Oligoadenylate synthetase-like (OASL) protein has been extensively characterized as a part of the anti-viral mechanism, however a number of transcriptomic studies reveal its upregulation in response to infection with a wide variety of intracellular bacterial pathogens. To date, there is no evidence documenting the role (if any) of OASL during mycobacterium tuberculosis infection. Using two pathogenic strains differing in virulence only, as well as the non-pathogenic M. bovis BCG strain, we observed that pathogenicity and virulence strongly induced OASL expression after 24 h of infection. Further, we observed that OASL knock down led to a significant increase in M. tb CFU counts 96 h post-infection in comparison to the respective controls. Luminex revealed that OASL silencing significantly decreased IL-1β, TNF-α and MCP-1 secretion in THP-1 cells and had no effect on IL-10 secretion. We therefore postulate that OASL regulates pro-inflammatory mediators such as cytokines and chemokines which suppress intracellular mycobacterial growth and survival.
The 2-deoxy-d-glucose-neutral red test and vagotomy : an experimental study
(HMPG, 1977-09) Van Rensburg, L. C. J.
The 2-deoxy-D-glucose neutral red test proved to be successful in assessing completeness of vagotomy in the baboon both intra- and postoperatively. There were no deleterious side-effects and we found that both products could be sterilized adequately. So far we have used this test on 5 patients in the immediate postoperative phase; in 1 patient, on whom the surgeon thought he had done an incomplete parietal cell vagotomy, the test was found to be positive within a week of the operation.
2020 WSES guidelines for the detection and management of bile duct injury during cholecystectomy
(BioMed Central, 2021-06-10) de Angelis, Nicola; Catena, Fausto; Memeo, Riccardo; Coccolini, Federico; Martínez-Pérez, Aleix; Romeo, Oreste M.; De Simone, Belinda; Di Saverio, Salomone; Brustia, Raffaele; Rhaiem, Rami; Piardi, Tullio; Conticchio, Maria; Marchegiani, Francesco; Beghdadi, Nassiba; Abu-Zidan, Fikri M.; Alikhanov, Ruslan; Allard, Marc-Antoine; Allievi, Niccolò; Amaddeo, Giuliana; Ansaloni, Luca; Andersson, Roland; Andolfi, Enrico; Azfar, Mohammad; Bala, Miklosh; Benkabbou, Amine; Ben-Ishay, Offir; Bianchi, Giorgio; Biffl, Walter L.; Brunetti, Francesco; Carra, Maria C.; Casanova, Daniel; Celentano, Valerio; Ceresoli, Marco; Chiara, Osvaldo; Cimbanassi, Stefania; Bini, Roberto; Coimbra, Raul; Luigi de’Angelis, Gian; Decembrino, Francesco; De Palma, Andrea; de Reuver, Philip R.; Domingo, Carlos; Cotsoglou, Christian; Ferrero, Alessandro; Fraga, Gustavo P.; Gaiani, Federica; Gheza, Federico; Gurrado, Angela; Harrison, Ewen; Henriquez, Angel; Hofmeyr, Stefan; Iadarola, Roberta; Kashuk, Jeffry L.; Kianmanesh, Reza; Kirkpatrick, Andrew W.; Kluger, Yoram; Landi, Filippo; Langella, Serena; Lapointe, Real; Le Roy, Bertrand; Luciani, Alain; Machado, Fernando; Maggi, Umberto; Maier, Ronald V.; Mefire, Alain C.; Hiramatsu, Kazuhiro; Ordoñez, Carlos; Patrizi, Franca; Planells, Manuel; Peitzman, Andrew B.; Pekolj, Juan; Perdigao, Fabiano; Pereira, Bruno M.; Pessaux, Patrick; Pisano, Michele; Puyana, Juan C.; Rizoli, Sandro; Portigliotti, Luca; Romito, Raffaele; Sakakushev, Boris; Sanei, Behnam; Scatton, Olivier; Serradilla-Martin, Mario; Schneck, Anne-Sophie; Sissoko, Mohammed L.; Sobhani, Iradj; Ten Broek, Richard P.; Testini, Mario; Valinas, Roberto; Veloudis, Giorgos; Vitali, Giulio C.; Weber, Dieter; Zorcolo, Luigi; Giuliante, Felice; Gavriilidis, Paschalis; Fuks, David; Sommacale, Daniele
ENGLISH ABSTRACT: Bile duct injury (BDI) is a dangerous complication of cholecystectomy, with significant postoperative sequelae for the patient in terms of morbidity, mortality, and long-term quality of life. BDIs have an estimated incidence of 0.4–1.5%, but considering the number of cholecystectomies performed worldwide, mostly by laparoscopy, surgeons must be prepared to manage this surgical challenge. Most BDIs are recognized either during the procedure or in the immediate postoperative period. However, some BDIs may be discovered later during the postoperative period, and this may translate to delayed or inappropriate treatments. Providing a specific diagnosis and a precise description of the BDI will expedite the decision-making process and increase the chance of treatment success. Subsequently, the choice and timing of the appropriate reconstructive strategy have a critical role in long-term prognosis. Currently, a wide spectrum of multidisciplinary interventions with different degrees of invasiveness is indicated for BDI management. These World Society of Emergency Surgery (WSES) guidelines have been produced following an exhaustive review of the current literature and an international expert panel discussion with the aim of providing evidence-based recommendations to facilitate and standardize the detection and management of BDIs during cholecystectomy. In particular, the 2020 WSES guidelines cover the following key aspects: (1) strategies to minimize the risk of BDI during cholecystectomy; (2) BDI rates in general surgery units and review of surgical practice; (3) how to classify, stage, and report BDI once detected; (4) how to manage an intraoperatively detected BDI; (5) indications for antibiotic treatment; (6) indications for clinical, biochemical, and imaging investigations for suspected BDI; and (7) how to manage a postoperatively detected BDI.
A 3-year survey of acute poisoning exposures in infants reported in telephone calls made to the Tygerberg Poison Information Centre, South Africa
(Health & Medical Publishing Group, 2016-03) Marks, Carine J.; Van Hoving, D. J.
ENGLISH ABSTRACT: Background. Infants undergo rapid development changes and are particularly vulnerable to toxic chemicals. Identifying and evaluating the toxic risks that exist in this age group could be very valuable when making recommendations on how to prevent specific types of poisoning. Objectives. This study analysed the toxic substances responsible for acute poisoning exposures in infants (<1 year of age) as well as the severity of the exposures. Methods. A retrospective analysis of the Tygerberg Poison Information Centre (TPIC) database was conducted over a 3-year period (1 January 2011 to 31 December 2013). Descriptive statistics are provided for the entire study population as well as for the neonatal subgroup (<30 days old). Results. The TPIC handled 17 434 consultations during the 3-year study period. Infants were involved in 1 101 cases (6.3%), of which 46 cases (4.2%) were neonates. Most enquiries about infants were associated with non-drug chemicals (n=824, 74.8%). Pharmaceuticals were involved in 185 cases (16.8%) followed by biological exposures (e.g. snake and spider bites, scorpion stings, plant and mushroom poisonings) (n=109, 9.9%). Most infants (n=987, 89.6%) presented with no or only minor symptoms. In neonates, 17 (37.0%) presented with moderate to severe toxicity. Six of these (35.3%) were poisoned by complementary and alternative medicines. Conclusion. Most poisoning exposures in infants are not serious and can be safely managed at home after contacting a poison centre. Identification and documentation of poisoning in this special population is of great importance.
38 years after its discovery, Ebola virus spins out of control
(South African Centre for Epidemiological Modelling and Analysis (SACEMA), 2014-09) Preiser, Wolfgang
The evolutionary origin of Ebolaviruses is not very clear. The simple notion that these viruses have been circulating for many millennia in wildlife in tropical parts of Africa, occasionally spilling over into human populations, often brought on by human activities, may not be correct or at least incomplete. Over time a number of Ebola disease outbreaks reported and a pattern in the outbreak response seemed to have been established. A lot was also learnt about Ebola viruses, their epidemiology and ecology. However, the 2014 Ebola outbreak challenges our understanding in many respects.
The 5-HTTLPR-rs25531 S-A-S-A haplotype and chronic stress moderate the association between acute stress and internalizing mental disorders among HIV+ children and adolescents in Uganda
(Frontiers, 2021-04-23) Kalungi, Allan; Womersley, Jacqueline S.; Kinyanda, Eugene; Joloba, Moses L.; Ssembajjwe, Wilber; Nsubuga, Rebecca N.; Seedat, Soraya, 1966-; Hemmings, Sian M.
Background: Internalizing mental disorders (IMDs) among HIV-positive (HIV+) children and adolescents are associated with poor disease outcomes, such as faster HIV disease progression. Although it has been suggested that the development of IMDs is moderated by interaction of stressful life events and vulnerability factors, the underlying etiology is largely unknown. Serotonin transporter gene [solute carrier family 6 member A4 (SLC6A4)] and human tryptophan hydroxylase 2 gene (TPH2) polymorphisms have been implicated in the development of IMDs. This study investigated the association between acute stress and IMDs, and moderation by chronic stress and genetic variants in SLC6A4 and TPH2. Hypothesis: Acute stress acts through genetic and environmental vulnerability factors to increase the risk of developing IMDs. Methods: Polymorphisms in SLC6A4 (5-HTTLPR, rs25531, 5-HTTLPR-rs25531, and STin2 VNTR) and TPH2 (rs1843809, rs1386494, rs4570625, and rs34517220) were genotyped in 368 HIV+ children and adolescents (aged 5–17 years) with any internalizing mental disorder (depression, anxiety disorders, or posttraumatic stress disorder), and 368 age- and sex-matched controls, who were also HIV+. Chronic and acute stress categories were derived by hierarchical cluster analysis. Logistic regression analysis was used to assess the independent moderating effect of chronic stress and each selected polymorphism on the association between acute stress and IMDs. Results: We observed a statistically significant association between severe acute stress and IMDs (p = 0.001). Children and adolescents who experienced severe acute stress were twice as likely to develop IMDs, compared to children and adolescents who experienced mild acute stress (p = 0.001). Chronic stress interacted with severe acute stress to increase the risk of IMDs (p = 0.033). Acute stress was found to interact with 5-HTTLPR-rs25531 S-A-S-A haplotype to increase the risk for IMDs among Ugandan HIV+ children and adolescents (p = 0.049). We found no evidence for a combined interaction of acute stress, chronic stress, and 5-HTTLPR-rs25531 on IMDs. Conclusion: The odds of having an internalizing mental disorder (IMD) were higher among HIV+ children and adolescents who experienced severe acute stress compared to HIV+ children and adolescents who experienced mild acute stress. Chronic stress and 5-HTTLPR-rs25531 independently moderated the association between acute stress and IMDs.
A 5-year analysis of the helicopter air mercy service in Richards Bay, South Africa
(Health & Medical Publishing Group, 2014-02) D'Andrea, Patrick Andrew; Van Hoving, Daniel Jacobus; Wood, Darryl; Smith, Wayne Patrick
Background. A helicopter emergency medical service (HEMS) was established in 2005 in Richards Bay, KwaZulu-Natal, South Africa, to provide primary response and inter-facility transfers to a largely rural area with a population of 3.4 million people. Objective. To describe the first 5 years of operation of the HEMS. Methods. A chart review of all flights from 1 January 2006 to 31 December 2010 was conducted. Results. A total of 1 429 flights were undertaken; 3 were excluded from analysis (missing folders). Most flights (88.4%) were inter-facility transfers (IFTs). Almost 10% were cancelled after takeoff. The breakdown by age was 61.9% adult, 15.1% paediatric and 21.6% neonate. The main indications for IFTs were obstetrics (34.5%), paediatrics (27.9%) and trauma (15.9%). For primary response most cases were trauma (72.9%) and obstetrics (11.3%). The median on-scene time for neonates was significantly longer (48 min, interquartile range (IQR) 35 - 64 min) than that for adults (36 min, IQR 26 - 48; p<0.001) and paediatrics (36 min, IQR 25 - 51; p<0.02). On-scene times for doctor-paramedic crews (45 min, IQR 27 - 50) were significantly longer than for paramedic-only crews (38 min, IQR 27 - 57; p<0.001). Conclusion. The low flight-to-population ratio and primary response rate may indicate under-utilisation of the air medical service in an area with a shortage of advanced life support crews and long transport distances. Further studies on HEMSs in rural Africa are needed, particularly with regard to cost-benefit analyses, optimal activation criteria and triage systems.
7-Year experience of transcatheter aortic valve implants (TAVI) in a Western Cape private healthcare setting
(South African Heart Association, 2019) Weich, Hellmuth; Liebenberg, Jacques; Van Wyk, Jacques; Vivier, Rocco; Barnard, Barry; Abelson, Mark; Phillips, Andre; Mabin, Tom
Introduction: We describe the largest South African transcatheter aortic valve implantation (TAVI) outcome report of a single team in the Western Cape, over a 7-year period from 2009 - 2016. Methods: All patients who received TAVI at Mediclinic Vergelegen and Mediclinic Panorama were prospectively entered into a database. A total of 244 implants (61 CoreValve and 183 Edwards valves) were performed. Results: Patients were high risk with a mean STS score of 7.89 (standard deviation (SD) 5.7) and mean logistic EuroSCORE of 26.5 (SD 12.5). There was a trend toward lower risk over time. Procedures were initially performed mainly via a transapical approach, but this changed to mostly transfemoral with the introduction of smaller delivery systems. Procedural success rate was 91.8% for CoreValve and 88.5% for Edwards cases. Mean length of hospital stay following TAVI was 9 days initially, but this declined to 4 days for the latter part of our experience. One year mortality was 19% and one year stroke rate was 10%. Conclusion: Despite the limitations of a study of this nature, our group could document outcomes similar to international studies, with improvements over time and illustrating successful cooperation between different hospitals to expand exposure and experience in a resource-constrained environment.
An 8-year retrospective study of adult and paediatric Burkitt’s lymphoma at Tygerberg Hospital, South Africa
(AOSIS, 2020-04-30) Musekwa, Ernest; Chapanduka, Zivanai C.; Bassa, Fatima; Kruger, Mariana
Background: Burkitt lymphoma(BL) is a high grade non-Hodgkin lymphoma, which may be underdiagnosed in South Africa, due to a high burden of infectious diseases such as HIV and TB which may present with similar clinical features. Aim: To describe demographics and clinico-pathological characteristics of patients diagnosed with BL. Setting: Tygerberg Hospital (TBH), South Africa between 2007-2014. Methods: We performed a retrospective descriptive and survival analysis of patients diagnosed with BL at TBH between 01 January 2007 and 31 December 2014 with at least 24-month follow-up. Data was collected from the Tygerberg Lymphoma Study Group database and the South African Children Cancer Study Group Tumour Registry. Results: There were 73 patients with BL, of whom 68 were admitted to TBH and whose data was further analysed. The majority of patients were adults (74%). There was a female predominance in adults and a male predominance in children (p = 0.002). Various regimens were used in adults while a single treatment protocol was used in children. The proportion of patients with HIV and advanced BL was higher in adults than in children. The 2-year overall survival of the treatment group was 45%. The outcome of patients with BL in adults (34%) was poorer than that of children (69%) (p = 0.022). HIV negative patients had a non-significant survival advantage (57%) over HIV positive patients with 41% 2-year overall survival (p = 0.2876). Conclusion: This study demonstrates a better cure rate in children treated for BL compared to adults, with HIV-infection being a risk factor for poor outcome.
An 8-year retrospective study of adult and paediatric Burkitt’s lymphoma at Tygerberg Hospital, South Africa
(AOSIS, 2020-04-30) Musekwa, Ernest; Chapanduka, Zivanai C.; Bassa, Fatima; Kruger, Mariana
Background: Burkitt lymphoma(BL) is a high grade non-Hodgkin lymphoma, which may be underdiagnosed in South Africa, due to a high burden of infectious diseases such as HIV and TB which may present with similar clinical features. Aim: To describe demographics and clinico-pathological characteristics of patients diagnosed with BL. Setting: Tygerberg Hospital (TBH), South Africa between 2007-2014. Methods: We performed a retrospective descriptive and survival analysis of patients diagnosed with BL at TBH between 01 January 2007 and 31 December 2014 with at least 24-month follow-up. Data was collected from the Tygerberg Lymphoma Study Group database and the South African Children Cancer Study Group Tumour Registry. Results: There were 73 patients with BL, of whom 68 were admitted to TBH and whose data was further analysed. The majority of patients were adults (74%). There was a female predominance in adults and a male predominance in children (p = 0.002). Various regimens were used in adults while a single treatment protocol was used in children. The proportion of patients with HIV and advanced BL was higher in adults than in children. The 2-year overall survival of the treatment group was 45%. The outcome of patients with BL in adults (34%) was poorer than that of children (69%) (p = 0.022). HIV negative patients had a non-significant survival advantage (57%) over HIV positive patients with 41% 2-year overall survival (p = 0.2876). Conclusion: This study demonstrates a better cure rate in children treated for BL compared to adults, with HIV-infection being a risk factor for poor outcome.
99mTc-MIBI stress-rest myocardial perfusion scintigraphy in patients with complete left bundle branch block
(2001) Ellmann, A.; Van Heerden, P. D. R.; Van Heerden, B. B.; Klopper, J. F.
Background. Patients with complete left bundle branch block (LBBB) often show a false-positive ischaemic pattern in the interventricular septum on thallium-201 (201Tl) stress-rest myocardial perfusion scintigraphy. Equivocal results have been reported with technetium-99m labelled hexakis-methoxyisobutyl isonitrile (99mTc-MIBI) in such patients. The aim of this retrospective study was to determine the effect of LBBB on the septal uptake of 99mTc-MIBI during stress-rest single photon emission computed tomography (SPECT) scintigraphy. Methods. We studied 75 consecutive patients with LBBB, referred for 99mTc-MIBI stress-rest SPECT. Studies were evaluated by visual analysis using a semi-quantitative grading technique. In all patients with abnormal septal segments, the presence or absence of ischaemic heart disease was confirmed either clinically or by means of angiographical examination. Results. Forty-three patients (57.3%) had completely normal studies. Only 15 (20%) had septal abnormalities (11 with reversible and 4 with fixed defects), while 17 patients (22.7%) had abnormal segments in areas other than the interventricular septum. Except for 1 patient lost to follow-up, ischaemic heart disease was confirmed in all the patients with septal changes. Conclusion. We conclude that 99mTc-MIBI is more specific than 201Tl for identifying ischaemic heart disease in the presence of LBBB.
A 3-year cytogenetic survey of 9661 patients in South Africa
(Health and Medical Publishing Group (HMPG), 1983) Bester, Rina; Benjamin, Mercy; Retief, A. E.; Bernstein, Renee; Grace, H. J.; Nelson, Matilda M.; Jansen, S.; Benjamin, Mercy
During the period 1 January 1977 - 31 December 1979, 9661 patients underwent cytogenetic investigation at seven participating laboratories in South Africa. The chromosome data were coded using a standard protocol and the results tabulated, being listed according to the clinical signs which led to referral for investigation. Cytogenetic investigation was most commonly requested for prenatal studies, and 22% of the group's effort was directed towards this. One in 27 amniotic cell specimens was reported to have shown anomalous chromosomes, trisomy 21 being the most frequent abnormality. The majority of postnatal investigations were requested because congenital abnormalities suggested an underlying chromosomal defect. In 42.3% of 2420 patients a chromosome defect was confirmed. Results of chromosome studies are tabulated by indication for referral and the findings summarized. This collaborative study gives an indication of the nature and frequency of chromosome disorders in South Africa.
Abacavir Exposure in Children Cotreated for Tuberculosis with Rifampin and Superboosted Lopinavir-Ritonavir
(2020-05) Rabie, Helena; Tikiso, Tjokosela; Lee, Janice
ABSTRACT In children requiring lopinavir coformulated with ritonavir in a 4:1 ratio (lopinavir-ritonavir-4:1) and rifampin, adding ritonavir to achieve a 4:4 ratio with lopi-navir (LPV/r-4:4) overcomes the drug-drug interaction. Possible drug-drug interac-tions within this regimen may affect abacavir concentrations, but this has never been studied. Children weighing 15 kg needing rifampin and LPV/r-4:4 were enrolled in a pharmacokinetic study and underwent intensive pharmacokinetic sampling on 3 visits: (i) during the intensive and (ii) continuation phases of anti-tuberculosis treatment with LPV/r-4:4 and (iii) 1 month after antituberculosis treat-ment completion on LPV/r-4:1. Pharmacometric modeling and simulation were used to compare exposures across weight bands with adult target exposures. Eighty-seven children with a median (interquartile range) age and weight of 19 (4 to 64) months and 8.7 (3.9 to 14.9) kg, respectively, were included in the abacavir analysis. Abacavir pharmacokinetics were best described by a two-compartment model with ﬁrst-order elimination and transit compartment absorption. After allometric scaling adjusted for the effect of body size, maturation could be identiﬁed: clearance was predicted to be fully mature at about 2 years of age and to reach half of this mature value at about 2 months of age. Abacavir bioavailability decreased 36% during treat-ment with rifampin and LPV/r-4:4 but remained within the median adult recom-mended exposure, except for children in the 3- to 4.9-kg weight band, in which the exposures were higher. The observed predose morning trough concentrations were higher than the evening values. Though abacavir exposure signiﬁcantly decreased dur-ing concomitant administration of rifampin and LPV/r-4:4, it remained within acceptable ranges. (This study is registered in ClinicalTrials.gov under identiﬁer NCT02348177.)
Abdominal ultrasound for diagnosing abdominal tuberculosis or disseminated tuberculosis with abdominal involvement in HIV-positive adults
(John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration, 2017) Van Hoving, Daniel J.; Meintjes, Graeme; Takwoingi, Yemisi; Griesel, Rulan; Maartens, Gary; Ochodo, Eleanor A.
This is a protocol for a Cochrane Review (Diagnostic test accuracy). The objectives are as follows: To determine the diagnostic accuracy of abdominal ultrasound as a standalone test for detecting abdominal TB or disseminated TB with abdominal involvement in HIV-positive adults. • To determine the diagnostic accuracy of combinations of abdominal ultrasound and existing tests (chest radiograph, full blood count) for detecting abdominal TB or disseminated TB with abdominal involvement in HIV-positive adults. • To investigate potential sources of heterogeneity in test accuracy, including clinical setting, ultrasound training level, and type of reference standard.
Abdominal ultrasound for diagnosing abdominal tuberculosis or disseminated tuberculosis with abdominal involvement in HIV-positive individuals
(John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration, 2019) Van Hoving, Daniel J.; Griesel, Rulan; Meintjes, Graeme; Takwoingi, Yemisi; Maartens, Gary; Ochodo, Eleanor A.
Background: Accurate diagnosis of tuberculosis in people living with HIV is difficult. HIV‐positive individuals have higher rates of extrapulmonary tuberculosis and the diagnosis of tuberculosis is often limited to imaging results. Ultrasound is such an imaging test that is widely used as a diagnostic tool (including point‐of‐care) in people suspected of having abdominal tuberculosis or disseminated tuberculosis with abdominal involvement. Objectives: To determine the diagnostic accuracy of abdominal ultrasound for detecting abdominal tuberculosis or disseminated tuberculosis with abdominal involvement in HIV‐positive individuals. To investigate potential sources of heterogeneity in test accuracy, including clinical setting, ultrasound training level, and type of reference standard. Search methods: We searched for publications in any language up to 4 April 2019 in the following databases: MEDLINE, Embase, BIOSIS, Science Citation Index Expanded (SCI‐EXPANDED), Social Sciences Citation Index (SSCI), Conference Proceedings Citation Index‐ Science (CPCI‐S), and also ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform to identify ongoing trials. Selection criteria: We included cross‐sectional, cohort, and diagnostic case‐control studies (prospective and retrospective) that compared the result of the index test (abdominal ultrasound) with one of the reference standards. We only included studies that allowed for extraction of numbers of true positives (TPs), true negatives (TNs), false positives (FPs), and false negatives (FNs). Participants were HIV‐positive individuals aged 15 years and older. A higher‐quality reference standard was the bacteriological confirmation of Mycobacterium tuberculosis from any clinical specimen, and a lower‐quality reference standard was a clinical diagnosis of tuberculosis without microbiological confirmation. We excluded genitourinary tuberculosis. Data collection and analysis: For each study, two review authors independently extracted data using a standardized form. We assessed the quality of studies using a tailored Quality Assessment of Diagnostic Accuracy Studies‐2 (QUADAS‐2) tool. We used the bivariate model to estimate pooled sensitivity and specificity. When studies were few we simplified the bivariate model to separate univariate random‐effects logistic regression models for sensitivity and specificity. We explored the influence of the type of reference standard on the accuracy estimates by conducting separate analyses for each type of reference standard. We assessed the certainty of the evidence using the GRADE approach. Main results: We included 11 studies. The risks of bias and concern about applicability were often high or unclear in all domains. We included six studies in the main analyses of any abnormal finding on abdominal ultrasound; five studies reported only individual lesions. The six studies of any abnormal finding were cross‐sectional or cohort studies. Five of these (83%) were conducted in low‐ or middle‐income countries, and one in a high‐income country. The proportion of participants on antiretroviral therapy was none (1 study), fewer then 50% (4 studies), more than 50% (1 study), and not reported (5 studies). The first main analysis, studies using a higher‐quality reference standard (bacteriological confirmation), had a pooled sensitivity of 63% (95% confidence interval (CI) 43% to 79%; 5 studies, 368 participants; very low‐certainty evidence) and a pooled specificity of 68% (95% CI 42% to 87%; 5 studies, 511 participants; very low‐certainty evidence). If the results were to be applied to a hypothetical cohort of 1000 people with HIV where 200 (20%) have tuberculosis then: ‐ About 382 individuals would have an ultrasound result indicating tuberculosis; of these, 256 (67%) would be incorrectly classified as having tuberculosis (false positives). ‐ Of the 618 individuals with a result indicating that tuberculosis is not present, 74 (12%) would be incorrectly classified as not having tuberculosis (false negatives). In the second main analysis involving studies using a lower‐quality reference standard (clinical diagnosis), the pooled sensitivity was 68% (95% CI 45% to 85%; 4 studies, 195 participants; very low‐certainty evidence) and the pooled specificity was 73% (95% CI 41% to 91%; 4 studies, 202 participants; very low‐certainty evidence). Authors' conclusions: In HIV‐positive individuals thought to have abdominal tuberculosis or disseminated tuberculosis with abdominal involvement, abdominal ultrasound appears to have 63% sensitivity and 68% specificity when tuberculosis was bacteriologically confirmed. These estimates are based on data that is limited, varied, and low‐certainty. The low sensitivity of abdominal ultrasound means clinicians should not use a negative test result to rule out the disease, but rather consider the result in combination with other diagnostic strategies (including clinical signs, chest x‐ray, lateral flow urine lipoarabinomannan assay (LF‐LAM), and Xpert MTB/RIF). Research incorporating the test into tuberculosis diagnostic algorithms will help in delineating more precisely its value in diagnosing abdominal tuberculosis or disseminated tuberculosis with abdominal involvement.

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