Regenerative medicines: A new regulatory paradigm for South Africa.

Clinicians are increasingly using regenerative medicines to repair, replace, regenerate or rejuvenate lost, damaged or diseased genes, cells, tissues or organs. In South Africa, access to these novel gene therapies and cell and tissue-based products is limited. The human leukocyte antigen (HLA) diversity and a paucity of suitable HLA-identical unrelated donors, results in limited access to haematopoietic stem and progenitor cell transplantation (HSPCT). Cell-based products could increase this access. Genetic diversity can also manifest in local or region-specific rare congenital disorders, and in vivo gene therapies hold the promise of developing treatments and cures for these debilitating disorders. South Africa has a disproportionate mortality rate due to non-natural causes, with many surviving with permanent injuries and disabilities. Tissue-engineered cell-based products have the potential to restore many of those affected and improve quality of life and productivity. These factors create an urgency for South Africa to develop regenerative medicines to address the country's unique needs and to provide access to these new and innovative treatment modalities. Achieving this objective requires a well-coordinated effort by multiple stakeholders and role players. A critical component of a regenerative medicine ecosystem is establishing an enabling regulatory framework for these new classes of medicines. Here we provide a brief profile of South Africa, including its genetic diversity, economy, the impact of the burden of disease, health policy and the healthcare system. We address the regulation of medicines, how the existing framework can accommodate regenerative medicines, and the steps needed to establish a future regulatory framework.

When cells become medicines: A South African perspective.

The discovery of human leucocyte antigen (HLA), serological matching and HLA-typing techniques, combined with the development of immunosuppressive medicines and improvements in infection control, have opened the way to cell, tissue and vascularised organ transplantation. Since the early 1960s, more than a million haematopoietic progenitor cell (HPC) transplantations have been performed worldwide to restore haematopoiesis and support immune system recovery after bone marrow ablation. HPC transplantation uses minimally manipulated autologous or allogeneic cells to restore the homologous functions of bone marrow. Research in biological sciences supported by new technologies is increasingly translated into therapeutic products intended to augment, repair, replace or regenerate genes, cells, tissues, organs and metabolic processes in the body. These products are referred to as regenerative medicine therapies or advanced therapy medicinal products, and include gene therapies, cell-based therapies and engineered tissue products.

Contact tracing during the COVID-19 pandemic: Protection of personal information in South Africa

Containing the COVID-19 pandemic necessitates the use of personal information without the consent of the person. The protection of personal information is fundamental to the rights that ensure an open and democratic society. When regulations that limit the right to privacy are issued outside of the democratic process, every effort must be made to protect personal information and privacy. The limitation of human rights must be treated as an exception to the norm, and any regulations should be drafted to ensure minimum limitation of rights, rather than to the minimum acceptable standard. The contact tracing regulations included in the COVID-19 disaster regulations include some basic principles to ensure privacy; however, other important principles are not addressed. These include principles of transparency and data security. The envisaged future use of human data for research purposes, albeit de-identified, needs to be addressed by the COVID-19 designated judge appointed under the regulations

Resource allocation during COVID-19: A focus on vulnerable populations

South Africa (SA) is a country of contrasts, with abundant resources, hard-won civil rights and a diverse population. Woven into the fabric of our society is a large divide between its poorest and its wealthiest members. In this article we highlight the vulnerabilities in our society that have been amplified by the COVID-19 crisis. Based on recent projections, it is very likely that the healthcare system will be overwhelmed. We acknowledge the recognition by government and civil society of these vulnerabilities, and note that difficult decisions will need to be made with regard to resource allocation. Our plea, however, is to ensure that human dignity and the principle of distributive justice are maintained, and that when difficult decisions are made, vulnerable people do not suffer disproportionately. Furthermore, it is of great concern that there is no national directive guiding resource allocation, prioritisation and triage decisions in both public and private hospitals. The Health Professions Council of SA should, as a matter of urgency, issue guidance on priority-setting and triage decisions in the context of COVID-19, based on distributive justice principles

Development of a Gene Expression Assay for the Diagnosis of Mycobacterium bovis Infection in African Lions (Panthera leo).

Mycobacterium bovis infection, the cause of bovine tuberculosis (BTB), is endemic in wildlife in the Kruger National Park (KNP), South Africa. In lions, a high infection prevalence and BTB mortalities have been documented in the KNP; however, the ecological consequences of this disease are currently unknown. Sensitive assays for the detection of this infection in this species are therefore required. Blood from M. bovis-exposed, M. bovis-unexposed, M. tuberculosis-exposed and M. bovis-infected lions was incubated in QuantiFERON® -TB Gold (QFT) tubes containing either saline or ESAT-6/CFP-10 peptides. Using qPCR, selected reference genes were evaluated for expression stability in these samples and selected target genes were evaluated as markers of antigen-dependent immune activation. The abundance of monokine induced by gamma interferon (MIG/CXCL9) mRNA, measured in relation to that of YWHAZ, was used as a marker of ESAT-6/CFP-10 sensitization. The gene expression assay results were compared between lion groups, and lenient and stringent diagnostic cut-off values were calculated. This CXCL9 gene expression assay combines a highly specific stimulation platform with a sensitive diagnostic marker that allows for discrimination between M. bovis-infected and M. bovis-uninfected lions.

Peyronie's disease--a perspective on the disease and the long-term results of radiotherapy.

From 1966 to 1988, 98 of 108 patients with symptomatic Peyronie's disease received radiotherapy at our institution. In 11 of 61 patients (18%) who attended the clinic regularly for follow-up for longer than a year, new lesions distinct from the original lesions developed. This confirms that there is progression of the disease in a substantial number of cases after treatment. Long-term follow-up over an average of 111.5 months was achieved by means of a questionnaire in 47 of the 98 cases (48%). Forty-one of these patients (87.2%) had sexual intercourse after radiation. Twenty-eight of the 41 (68.3%) still have intercourse. Their average age at present is 59.6 years while the average age of the 13 patients (31.7%) not having intercourse is 70.9 years. The decline in sexual activity is thus age-related. Twenty-one of 25 patients (84%) experienced relief from pain, and angulation of the penis improved in 17 of 44 patients (38.6%) after radiotherapy. Radiotherapy may therefore be of benefit to patients with active Peyronie's disease and should be investigated in a randomised controlled study.

Changes in penile skin blood flow following intracavernosal injection of papaverine.

Marked changes in penile skin blood flow following intracavernosal injection of papaverine were observed in 14 subjects. Increased flow was more pronounced in those patients who failed to achieve erection or had poor erection than in those who responded with adequate erection. This observation may explain in part why papaverine fails in subjects responding to prostaglandin E1. It raises the suspicion of a corporal cutaneous shunt, which may influence the choice between the use of an external vacuum device and venous surgery in certain cases of venogenic impotence.

Continent vesicostomy with an ileal conduit. A case report.

A patient is described who had construction of a vesicocutaneous ileal conduit with a continent intussusception valve allowing for intermittent self-catheterisation. The procedure was performed on a 13-year-old male patient with a normal bladder but with a totally unreconstructable urethra as a result of previous traumatic urethral disruption and unsuccessful urethral alignment procedures.

Megacyst of the penis.

A neonate presented with a penis 23 cm. long and 5 cm. in diameter. The relevant embryology of the penis is reviewed and a possible explanation for the anomaly is presented.