South African Medical Journal - Volume 102, Issue 6, 2012
Volumes & issues
Volume 102, Issue 6, 2012
No health without mental health : establishing psychiatry as a major discipline in an African Faculty of Health Sciences : forum - reflectionsSource: South African Medical Journal 102, pp 449 –451 (2012)More Less
Psychiatry has not always been a major clinical discipline in medical schools. Although the Faculty of Health Sciences of the University of Cape Town (UCT) celebrates its Centenary in 2012, a closely aligned major psychiatric hospital is older than the Medical School, while the Department of Psychiatry is only 50 years old. These differing dates reflect the history of and challenge for psychiatry; mental disorders contribute a major portion of the burden of disease, while appropriate recognition and resourcing of services and training has been delayed. There are ongoing challenges in aligning the visions of an old state-run system that focused on those with severe psychotic illness, a newer governmental vision of the importance of treating mental disorders in the community, the realities of current under-resourcing, and the international aspiration that psychiatry is one of the clinical neurosciences. Nevertheless, considerable strides have been made towards moving psychiatry from the periphery of society and medicine to a central discipline within the Faculty of Health Sciences at UCT.
South African HIV-1 vaccine candidates - the journey from the bench to clinical trials : forum - reflectionsSource: South African Medical Journal 102, pp 452 –455 (2012)More Less
Around 2.5 million people become infected with human immunodeficiency virus (HIV) each year. This extraordinary toll in human life and public health worldwide will only be reversed with effective prevention. Vaccination is regarded as the most effective way to prevent infectious disease. However, there are many challenges to overcome before a successful prophylactic HIV vaccine will be available.
We are participating in a global effort to develop and test candidate HIV vaccines. Two candidate prophylactic HIV vaccines that were designed and developed at the University of Cape Town (UCT) entered phase 1 clinical trials in the USA and South Africa in 2009, after a 9-year development period. In addition to the vaccines in clinical trial, there is a pipeline of candidate HIV-1 subtype C vaccines including virus-like particles, novel DNA vaccines, capripoxvirus and Bacillus Calmette-Guérin (BCG)-vectored vaccines. This article describes the history of HIV vaccine research at UCT, and the partnerships that made the project possible.
Biomedical engineering at the University of Cape Town - challenges and opportunities : forum - reviewSource: South African Medical Journal 102 (2012)More Less
The biomedical engineering programme at the University of Cape Town has the potential to address some of South Africa's unique public health challenges and to contribute to growth of the local medical device industry, directly and indirectly, through research activities and postgraduate education. Full realisation of this potential requires engagement with the clinical practice environment and with industry.
Approaches to target identification and validation for tuberculosis drug discovery : a University of Cape Town perspective : forum - reviewSource: South African Medical Journal 102, pp 457 –460 (2012)More Less
Tuberculosis (TB) disproportionately affects a few high-burden countries including South Africa. In these regions, basic TB research is rare, endemic countries being valued primarily as sites for drug trials and clinical studies. Our basic mycobacterial research focuses on current approaches to drug target identification and validation within the context of international trends in TB drug discovery. Increased funding for TB drug development globally prompted a significant shift in the composition of drug discovery consortia, with academic laboratories assuming a major role in collaboration with industrial partners. This hybrid model holds promise for the expansion of local programmes, especially where actively supported by government. However, the application of industry-standard business practices to research projects involving biology and chemistry expertise demands a greater appreciation of the differences between a chemically, versus biologically, validated drug target, and of the factors informing these differences.
Shedding the load of hypertension : the proteolytic processing of angiotensin-converting enzyme : forum - reviewSource: South African Medical Journal 102, pp 461 –464 (2012)More Less
A number of membrane proteins are enzymatically cleaved or 'shed' from the cell surface, resulting in the modulation of biological events and opening novel pharmaceutical approaches to diverse diseases by targeting shedding. Our focus has been on understanding the shedding of angiotensin-converting enzyme (ACE), an enzyme that plays a pivotal role in blood pressure regulation. The identification of novel hereditary ACE mutations that result in increased ACE shedding has advanced our understanding of the role of ACE shedding in health and disease. Extensive biochemical and molecular analysis has helped to elucidate the mechanism of ACE shedding. These findings point to the potential therapeutic role of targeting shedding in regulating tissue ACE levels in cardiovascular disease.
Source: South African Medical Journal 102, pp 465 –468 (2012)More Less
South Africa is in the midst of the world's largest human immune deficiency virus (HIV) epidemic with an estimated 5.6 million people infected. Haematological manifestations of HIV are common and diverse, occurring at all stages of infection. Haematological emergencies occurring in this setting include the high-grade lymphomas, particularly Burkitt lymphoma, and thrombotic thrombocytopenic purpura (TTP). Immune thrombocytopenic purpura (ITP), opportunistic infections and drug side-effects are also frequent causes of cytopenias. A bone marrow biopsy has a high diagnostic utility in HIV patients presenting with unexplained cytopenias and/or fevers. It is not widely realised that HIV is also a prothrombotic state with an increased incidence of thromboembolic disease. Highly active antiretroviral therapy (HAART) is now widely available in South Africa and is a crucial adjunct to therapy of haematological complications. Medical professionals across all disciplines need to be alert to the haematological complications of HIV infection.
Masithethe : speech and language development and difficulties in isiXhosa : forum - clinical practiceSource: South African Medical Journal 102, pp 469 –471 (2012)More Less
IsiXhosa is the second most spoken language in South Africa and one of its official languages. Spoken mainly in the Eastern and Western Cape regions it is fitting that much of the research focusing on children's isiXhosa speech and language acquisition has been carried out at the University of Cape Town. We describe what is known about children's acquisition of isiXhosa, and highlight studies which inform our knowledge of the typical development of the language in relation to the acquisition of consonants including clicks and the isiXhosa noun class system. Little is known about the specific nature of speech and language difficulties in isiXhosa, and the development of isiXhosa resources for speech and language assessment and therapy is in its infancy. Suggestions are made for advancing knowledge and practice which is needed to provide a relevant and quality service to isiXhosa speakers.
Source: South African Medical Journal 102, pp 472 –473 (2012)More Less
A 24-year-old black female (HIV-positive) was referred to our clinic with a 4-week history of an ulcerative lesion of the right upper and lower eyelids. She was on treatment for pulmonary tuberculosis and had been admitted to a secondary level hospital. She had no other ocular symptoms or signs. A tissue biopsy of the lesion revealed multinucleate squamous cells with ground glass viral nuclear inclusion bodies, indicative of herpes simplex virus (HSV) infection. The ulcer healed with oral and topical acyclovir therapy, confirming a herpetic origin. There is only one other reported case of this type of ulcerative eyelid lesion caused by HSV; the patient in this case was also immunocompromised.
Source: South African Medical Journal 102, pp 474 –476 (2012)More Less
We present a case and discuss stroke related to human immunodeficiency virus (HIV) infection and the difficulties of reaching a firm diagnosis of the cause of the aneurysmal vasculopathy. In the absence of a clear aetiology we suggest looking for varicella zoster virus (VZV) replication in the cerebrospinal fluid (CSF) by polymerase chain reaction (PCR) and treating with intravenous acyclovir, aiming for HIV control with appropriate antiretroviral therapy and providing suitable antiplatelet agents. If there is a high index of suspicion of VZV, therapy with acyclovir may be prudent even if the CSF PCR is negative (as may occur after the first 2 weeks of reactivation of infection). Determination of a VZV plasma:CSF IgG ratio is not readily available and would only provide surrogate support for a previous VZV infection in the central nervous system compartment.
Health Sciences undergraduate education at the University of Cape Town : a story of transformation : forum - educationSource: South African Medical Journal 102, pp 477 –480 (2012)More Less
Undergraduate education and training in the Faculty of Health Sciences at the University of Cape Town has become socially responsive. A story of transformation that is consonant with wider societal developments since the 1994 democratic elections, outlining the changes in undergraduate curricula across the Faculty, is presented.
Source: South African Medical Journal 102, pp 481 –484 (2012)More Less
Polyglutamine diseases are inherited neurodegenerative conditions arising from expanded trinucleotide CAG repeats in the disease-causing gene, which are translated into polyglutamine tracts in the resultant protein. Although these diseases share a common type of mutation, emerging evidence suggests that pathogenesis is complex, involving disruption of key cellular pathways, and varying with the disease context.
An understanding of polyglutamine disease mechanisms is critical for development of novel therapeutics. Here we summarise theories of molecular pathogenesis, and examine ways in which this knowledge is being harnessed for therapy, with reference to work under way at the University of Cape Town. Despite a plethora of preclinical data, clinical trials of therapies for polyglutamine diseases have had only limited success. However, recently initiated trials, including those using gene silencing approaches, should provide valuable insights into the safety and efficacy of therapies directly targeting polyglutamine pathogenesis. This is particularly relevant in the South African context, where the frequencies of 2 polyglutamine diseases, spinocerebellar ataxia types 1 and 7, are among the highest globally.
Author Hanna-Andrea RotherSource: South African Medical Journal 102, pp 485 –488 (2012)More Less
An effective surveillance system is required to reduce pesticide exposures and poisonings, especially from street pesticides (illegal, unlabelled, and decanted agricultural pesticides used predominately for urban household purposes). Poisoning from any pesticide class, not only organophosphates, constitutes a medically notifiable condition in South Africa. Current practice, however, is to report only organophosphate cases, resulting in severe under-reporting. The lack of data concerning the link between poisonings and street pesticides has led to the mistaken assumption that urban populations are not at risk from significant pesticide exposures and poisonings. Without accurate statistics, healthcare professionals and policy makers are unaware of the contribution of street pesticide poisonings to the overall health burden. Accurate diagnosis is a prerequisite for notification and subsequent surveillance. An algorithm has been developed to enable healthcare professionals to improve the diagnosis and notification of pesticide poisonings.
What healthcare financing changes are needed to reach universal coverage in South Africa? : forum - analysisAuthor Diane McIntyreSource: South African Medical Journal 102, pp 489 –490 (2012)More Less
The national health insurance proposed for South Africa aims to achieve a universal health system. The best way to identify the financing mechanism that is best suited to achieving this goal is to consider international evidence on funding in universal health systems. The evidence from Organisation for Economic Cooperation and Development countries and a number of middle-income countries that have achieved universal coverage clearly indicates that mandatory pre-payment financing mechanisms (i.e. general tax funding, in some cases supplemented by mandatory health insurance) must dominate, with a clearly specified, complementary role for voluntary or private health insurance.
Source: South African Medical Journal 102, pp 491 –492 (2012)More Less
Starting millions of years ago, the heart developed metabolic and molecular cardioprotective paths. The concept of metabolic protection includes the recent successful early provision of glucose-insulin-potassium (GIK) to patients with acute coronary syndromes in the ambulance to inhibit high harmful free-fatty acid levels. Molecular cardioprotective pathways also developed in primeval times. The 2 major paths are the RISK (Reperfusion Injury Salvage Kinases) path and the SAFE (Survival Activating Factor Enhancement) path, on which our group in Cape Town has focused. These paths help to lessen ischaemic-perfusion damage, and may, hypothetically, also be activated by intense exercise.
Inflammatory pathways in cervical cancer - the University of Cape Town's contribution : forum - analysisSource: South African Medical Journal 102, pp 493 –496 (2012)More Less
Cervical cancer is the leading gynaecological malignancy in southern Africa. The main causal factor for development of the disease is infection of the cervix with human papillomavirus. It is a multi-step disease with several contributing co-factors including multiple sexual partners, a compromised immune system and cervical inflammation caused by infections with Chlamydia trachomatis or Neisseria gonorrhoeae. Inflammation involves extensive tissue remodelling events which are orchestrated by complex networks of cytokines, chemokines and bio-active lipids working across multiple cellular compartments to maintain tissue homeostasis. Many pathological disorders or diseases, including cervical cancer, are characterised by the exacerbated activation and maintenance of inflammatory pathways. In this review we highlight our findings pertaining to activation of inflammatory pathways in cervical cancers, addressing their potential role in pathological changes of the cervix and the significance of these findings for intervention strategies.
Source: South African Medical Journal 102, pp 497 –498 (2012)More Less
HIV infection was previously an absolute contraindication to renal transplantation. However, with the advent of highly active antiretroviral therapy (HAART), renal transplantation using HIV-negative donor kidneys has successfully been employed for HIV-infected patients with end-stage renal failure. In resource-limited countries, places on dialysis programmes are severely restricted; HIV-infected patients, like many others with co-morbidity, are often denied treatment. Kidneys (and other organs) from HIV-infected deceased donors are discarded. The transplantation of HIV-positive donor kidneys to HIV-infected recipients is now a viable alternative to chronic dialysis or transplantation of HIV-negative donor kidneys. This significantly increases the pool of donor kidneys to the advantage of HIV-positive and -negative patients. Arguments are presented that led to our initiation of renal transplantation from HIV-positive deceased donors to HIV-positive recipients at Groote Schuur Hospital, Cape Town.
The prevalence and burden of pain and other symptoms among South Africans attending HAART clinics : researchSource: South African Medical Journal 102, pp 499 –500 (2012)More Less
Background. Since the advent of antiretrovirals, HIV disease has largely come to be considered a chronic disease for those able to access treatment. As such, the concept of 'living well' with HIV is important. Increasing evidence suggests a high symptom burden in HIV that persists in the presence of treatment.
Objectives. Our study aimed to measure the prevalence and burden of pain and other physical and psychological symptoms among South African HIV-positive patients attending highly active antiretroviral therapy (HAART) clinics.
Methods. The study design was a cross-sectional survey. Simple random sampling was used to recruit 385 adult participants.
Results. The sample had a median age of 40 years (Q1 - Q3=33 - 46) and 98.4% were receiving HAART. The mean latest CD4 count for the participants was 355.06±219/mm3. The mean number of symptoms of the 32 symptoms on the MSAS-SF experienced by participants was 10.24±5.71 (range 1 - 28). All 4 psychological symptoms were in the top 10 most prevalent symptoms, with feeling sad being the most prevalent symptom overall.
Conclusions. The high prevalence of symptoms and the high symptom burden experienced by the participants in this survey suggest inadequate symptom control and highlight the palliative care needs of an ambulant patient population already receiving HAART. Extension of life without reasonable efforts to also address the patient's quality of life is not ethically justifiable. In addition, more research appears to be required to answer whether these findings are associated with sub-optimal HAART adherence.
Remote sensing of HIV care programmes using centrally collected laboratory results : can we monitor ART programme effectiveness? : researchSource: South African Medical Journal 102, pp 501 –505 (2012)More Less
Aims. We describe a monitoring system at population level of patients on antiretroviral therapy (ART) using centrally collected laboratory data. We demonstrate an analogous process of remote sensing using a large set of laboratory results and illustrate the tremendous density of information stored. We moved from an individual to a community view of ART rollout, similar to remote sensing used in the earth and biological sciences when the spatial scale of the investigation is too large to be performed at ground level.
Methods. This was a retrospective cohort study of patients from January 2004 to June 2011. A total of 188 759 individual laboratory results representing 26 445 patients were analysed for average CD4 and viral load by year.
Results. The data showed an increasing state of health of the population and allowed for hypothesis generation when the trends did not follow expected paths.
Conclusion. In this analysis we moved away from individual-centred data to population-level data in order to assess ART programme performance. Routine patient-monitoring data had great utility in assessment of population health. These methods are useful in monitoring and evaluation and effectiveness studies as they are easy to collect, reliable (not requiring much human matching or interventions) and scalable from a single clinic to an entire population. The larger the sample size, the more reliable the results, as confounders (such as incorrectly identified transfers out, lost-to-follow-up patients and transfers in) would be removed.
Burden of antituberculosis and antiretroviral drug-induced liver injury at a secondary hospital in South Africa : researchAuthors: Charlotte Schutz, Suzaan Marais, Rosie Burton, Chris Kenyon, Gary Maartens, Robert J. Wilkinson, Graeme Meintjes, Charlotte Schutz, Zahiera Ismail, Charles John Proxenos, Suzaan Marais, Rosie Burton, Chris Kenyon, Robert J. Wilkinson, Graeme Meintjes, Robert J. Wilkinson, Graeme Meintjes and Robert J. WilkinsonSource: South African Medical Journal 102, pp 506 –511 (2012)More Less
Background. G F Jooste Hospital (GFJH) is a secondary-level referral hospital in a high HIV and tuberculosis (TB) co-infection setting.
Aims. To assess the proportion of significant drug-induced liver injury (DILI) due to tuberculosis treatment (TBT) and/or antiretroviral therapy (ART) among patients presenting with liver dysfunction at GFJH and to describe management and outcomes.
Methods. A retrospective observational study was performed of all cases referred to GFJH with significant liver dysfunction from 1 January to 30 June 2009. Significant liver dysfunction was defined by alanine transaminase (ALT)≥200 U/l or total bilirubin (TBR)≥44 µmol/l. TBT- or ART-associated DILI was defined as significant liver dysfunction attributed to TBT and/or ART and which resulted in the halting of treatment or the adjustment thereof. Outcome measures included case numbers, descriptive data, and in-hospital and 3-month mortality.
Results. A total of 318/354 cases of significant liver dysfunction were reviewed: 71 were classified as TBT- or ART-associated DILI, while liver dysfunction was attributed to other causes in the remainder. In-hospital and 3-month mortality of TBT- or ART-associated DILI patients was 27% (n=19) and 35% (n=25), respectively. The majority of deaths were related to sepsis or sepsis complicating liver dysfunction. Twenty-three patients (32%) were lost to follow-up; 23 (32%) were alive and in outpatient care 3 months after presentation.
Conclusions. TBT- or ART-associated DILI is a common reason for presentation at a referral hospital in South Africa. In-hospital and 3-month mortality are high. Prospective studies are needed to define optimal management.
Source: South African Medical Journal 102, pp 512 –517 (2012)More Less
Background. Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an early complication of combination antiretroviral therapy (cART). Two forms are recognised: (i) paradoxical - recurrent or new TB symptoms develop after cART initiation in patients receiving TB treatment prior to cART; and (ii) unmasking TB-IRIS - active TB presents within 3 months of cART in patients not receiving TB treatment at cART initiation. The latter has heightened clinical manifestations and a marked inflammatory presentation.
Aim. To gain insight into the immune pathogenesis of a case of unmasking TB-IRIS.
Methods. The patient was recruited when starting cART and followed up at 4, 12 and 24 weeks of treatment. Peripheral blood mononuclear cells were used for flow cytometry.
Results. Immunological analysis indicated increased CD4+ T-cell proportions from 1.1% at baseline to 14% at 24 weeks (the CD4 count increased from 4 cells/µl at baseline to 41 cells/µl at 24 weeks). HIV viral load fell from 460 774 to 1 405 copies/ml during the same period. The proportion of TB antigen (PPD)-specific CD4+IFN-γ+ cells increased from 0.4% at baseline and 4 weeks (IRIS onset) to 7.8% at 12 weeks (after resolution of the IRIS episode); this fell to 0.7% at 24 weeks. The surface phenotype of CD4+IFN-γ+ cells during the episode was CD45RO+, CD45RA-, CCR7-, CD62L-, CCR5+/- and CD69-. We found a distorted balance between central memory and effector memory T-cells at cART commencement that might have predisposed the patient to unmasking TB-IRIS. We showed that this might have reflected compromised thymic output.
Discussion. While it has been suggested that tuberculin-specific Th1-responses induce TB-IRIS in HIV co-infected patients, our data in this case indicated that these cells were expanded only after IRIS onset and were therefore not inducing TB-IRIS.
Conclusion. We describe, in hitherto unpublished detail, the immunological characterisation of an unmasking TB-IRIS case; we show that thymic output may be compromised at IRIS onset.