Akin Abayomi

Diagnosis and management of lymphomas and other cancers in HIV-infected patients

Despite the introduction of highly active antiretroviral therapy or combination antiretroviral therapy (HAART and cART, respectively) patients infected with HIV might develop certain types of cancer more frequently than uninfected people. Lymphomas represent the most frequent malignancy among patients with HIV. Other cancer types that have increased in these patients include Kaposi sarcoma, cancer of the cervix, anus, lung and liver. In the post-HAART era, however, patients with HIV have experienced a significant improvement in their morbidity, mortality and life expectancy. This Review focuses on the different types of lymphomas that generally occur in patients with HIV. The combination of cART and antineoplastic treatment has resulted in remarkable prolongation of disease-free survival and overall survival among patients with HIV who develop lymphoma. However, the survival in these patients still lags behind that of patients with lymphoma who are not infected with HIV. We also provide an update of epidemiological data, diagnostic issues, and strategies regarding the most-appropriate management of patients with both HIV and lymphomas.

The H3Africa policy framework: negotiating fairness in genomics

Human Heredity and Health in Africa (H3Africa) research seeks to promote fair collaboration between scientists in Africa and those from elsewhere. Here, we outline how concerns over inequality and exploitation led to a policy framework that places a firm focus on African leadership and capacity building as guiding principles for African genomics research.

Challenges of Biobanking in South Africa to Facilitate Indigenous Research in an Environment Burdened with Human Immunodeficiency Virus, Tuberculosis, and Emerging Noncommunicable Diseases

The high burden of infectious diseases and the growing problem of noncommunicable and metabolic disease syndromes in South Africa (SA) forces a more focused research approach to facilitate cutting-edge scientific growth and public health development. Increased SA research on these diseases and syndromes and the collection of associated biospecimens has ensured a plethora of biobanks created by individuals, albeit without the foresight of prospective and collective use by other local and international researchers. As the need for access to high-quality specimens in statistically relevant numbers has increased, so has the necessity for the development of national human biobanks in SA and across the Continent. The prospects of achieving sustainable centralized biobanks are still an emerging and evolving concept, primarily and recently driven by the launch of the H3Africa consortium, which includes the development of harmonized and standardized biobanking operating procedures. This process is hindered by a myriad of complex societal considerations and ethico-legal challenges. Efforts to consolidate and standardize biological sample collections are further compromised by the lack of full appreciation by national stakeholders of the biological value inherent in these collections, and the availability of high quality human samples with well-annotated data for future scientific research and development. Inadequate or nonexistent legislative structures that specifically regulate the storage, use, dispersal, and disposal of human biological samples are common phenomena and pose further challenges. Furthermore, concerns relating to consent for unspecified future uses, as well as access to information and data protection, are all new paradigms that require further consideration and public engagement. This article reviews important fundamental issues such as governance, ethics, infrastructure, and bioinformatics that are important foundational prerequisites for the establishment and evolution of successful human biobanking in South Africa.

Addressing ethical issues in H3Africa research – the views of research ethics committee members

In June 2014, the H3Africa Working Group on Ethics organised a workshop with members of over 40 research ethics committees from across Africa to discuss the ethical challenges raised in H3Africa research, and to receive input on the proposed H3Africa governance framework. Prominent amongst a myriad of ethical issues raised by meeting participants were concerns over consent for future use of samples and data, the role of community engagement in large international collaborative projects, and particular features of the governance of sample sharing. This report describes these concerns in detail and will be informative to researchers wishing to conduct genomic research on diseases pertinent to the African research context.

Critical Issues in International Biobanking

Biobanking for clinical or research purposes includes the collection, processing, storage, and analysis of biological specimens. It is now well recognized that biobanking involves a complex array of technical and ethical/regulatory considerations. Biobanking policies and procedures are often documented by best practices that are usually voluntary but may be supplemented and reinforced by strict rules and regulations that govern informed consent, privacy, QC, and other critical issues. As biobanking has emerged as a global endeavor, with national networks and international collaboration becoming the norm, it has become even more critical that practices are coordinated and that quality standards are developed. Biobanking is also often a business endeavor, in that formal strategic and business plans need to be developed to ensure the long-term survival of the associated research programs. As new technologies are developed for using biospecimens to diagnose and treat disease, as well as to evaluate genetic risks, patients are becoming more aware of the importance and benefits of biobanking as part of the medical infrastructure. As a result, patients who donate biospecimens are becoming more interested in learning more about their own samples use and in seeing the actual results of the research. One of the aspects of these evolving attitudes toward biobanking was addressed in a previous QA Clin Chem 57:540–4). From the broad array of issues that could be addressed, this Q&A focuses on a few critical issues that many biobanks are facing today: quality management, biobank network design, long-term sustainability, conveying the importance of biobanking to the public, and the return of research results to biospecimen donors. Five experts who are engaged in national and international biobanking programs discuss these complex issues here. What are some of the important issues related to …

A perpetual source of DNA or something really different: ethical issues in the creation of cell lines for African genomics research

BackgroundThe rise of genomic studies in Africa – not least due to projects funded under H3Africa – is associated with the development of a small number of biorepositories across Africa. For the ultimate success of these biorepositories, the creation of cell lines including those from selected H3Africa samples would be beneficial. In this paper, we map ethical challenges in the creation of cell lines.DiscussionThe first challenge we identified relates to the moral status of cells living in culture. There is no doubt that cells in culture are alive, and the question is how this characteristic is relevant to ethical decision-making. The second challenge relates to the fact that cells in culture are a source of cell products and mitochondrial DNA. In combination with other technologies, cells in culture could also be used to grow human tissue. Whilst on the one hand, this feature increases the potential utility of the sample and promotes science, on the other it also enables further scientific work that may not have been specifically consented to or approved. The third challenge relates to ownership over samples, particularly in cases where cell lines are created by a biobank, and in a different country than where samples were collected. Relevant questions here concern the export of samples, approval of secondary use and the acceptability of commercialisation. A fourth challenge relates to perceptions of blood and bodily integrity, which may be particularly relevant for African research participants from certain cultures or backgrounds. Finally, we discuss challenges around informed consent and ethical review.SummaryIn this paper, we sought to map the myriad of ethical challenges that need to be considered prior to making cell line creation a reality in the H3Africa project. Considering the relative novelty of this practice in Africa, such challenges will need to be considered, discussed and potentially be resolved before cell line creation in Africa becomes financially feasible and sustainable. We suggest that discussions need to be undertaken between stakeholders internationally, considering the international character of the H3Africa project. We also map out avenues for empirical research.

Taking the bull by the horns: Ethical considerations in the design and implementation of an Ebola virus therapy trial

Abstract Ebola virus is categorized as one of the most dangerous pathogens in the world. Although there is no known cure for Ebola virus, there is some evidence that the severity of the disease can be curtailed using plasma from survivors. Although there is a general consensus on the importance of research, methodological and ethical challenges for conducting research in an emergency situation have been identified. Performing clinical trials is important, especially for health conditions that are of public health significance (including rare epidemics) to develop new therapies as well as to test the efficacy and effectiveness of new interventions. However, routine clinical trial procedures can be difficult to apply in emergency public health crises hence require a consideration of alternative approaches on how therapies in these situations are tested and brought to the market. This paper examines some of the ethical issues that arise when conducting clinical trials during a highly dangerous pathogen outbreak, with a special focus on the Ebola virus outbreak in West Africa. The issues presented here come from a review of a protocol that was submitted to the Global Emerging Pathogens Treatment Consortium (GET). In reviewing the proposal, which was about conducting a clinical trial to evaluate the safety and efficacy of using convalescent plasma in the management of Ebola virus disease, the authors deliberated on various issues, which were documented as minutes and later used as a basis for this paper. The experiences and reflections shared by the authors, who came from different regions and disciplines across Africa, present wide-ranging perspectives on the conduct of clinical trials during a dangerous disease outbreak in a resource-poor setting.

Convalescent plasma and the dose of Ebola virus antibodies

n engl j med 376;13 nejm.org March 30, 2017 1296 fective therapy should not preclude physicians from diagnosing acute kidney injury accurately; in many parts of the developing world, ready access to laboratory testing of serum or plasma is limited, whereas assessment of urine output is readily available and inexpensive.1 Two recent studies of pediatric acute kidney injury in India did not use urine output criteria for the diagnosis of acute kidney injury and may have missed the diagnosis in some cases.2,3 We agree that the presence of baseline data on serum creatinine concentrations 3 months before enrollment could reflect an underlying chronic illness associated with chronic kidney disease, as we noted in Table S3a in the Supplementary Appendix. Choy and Choy point out that different assay methods for the measurement of plasma creatinine may lead to different absolute results; however, acute kidney injury is defined by changes in plasma creatinine in the KDIGO criteria, and therefore as long as the assay used is the same within each center, there should be no concern when assessing whether a change in the level has occurred. We used the original Schwartz formula to calculate estimated creatinine clearance, because this was the version validated in the literature for this purpose.4 The correspondents add to the argument we make about the importance of understanding the effect of acute kidney injury in children when they note that current methods for the measurement of creatinine vary across institutions and countries. More importantly, as compared with that in an adult, the creatinine concentration in a child is affected by many factors, which leads to imprecise and wideranging normal values.

Convalescent Ebola plasma: assessing neutralizing antibodies at the right stage

Convalescent Ebola plasma: assessing neutralizing antibodies at the right stage T. Burnouf, J. M. Dye, J. Ambe, A. Abayomi & Global Emerging Pathogens Treatment Consortium (GET) Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan US Army Medical Research Institute of Infectious Diseases, Fort Detrick, MA, USA GET, Mainland Hospital, 1 Mainland Hospital Road, Yaba, Lagos, Nigeria Stellenbosch University, Faculty of Medicine and Health Sciences and the National Health Laboratory Services, Tygerberg Hospital, Cape Town

A107 Lymphoma incidence and HIV-related lymphoma subtypes seen at Tygerberg Academic Hospital, Western Cape, South Africa, 2002-2011

Background:The incidence of lymphomas in the Western Cape, a province of South Africa, with a population of 5 million and a HIV prevalence of 17% is undocumented. Antiretroviral therapy (ART) was introduced into the public patient sector in 2004 with 34% estimated coverage by 2010. People living with HIV (PLWH) have a significant increased risk of developing HIV-related lymphoma (HRL). Therefore, HRL would be expected to increase but retard with introduction of ART. The pattern of the impact of HIV and effect of introduction of ART is investigated. Methods:We reviewed all patients diagnosed with malignant lymphoma (ML) from the Tygerberg Hospital catchments area in the Western Cape of South Africa for years 2002-2011. In this time frame 900 cases of ML were identified of which 710 were HIV negative and 190 HIV positive. ML were sub-typed according to WHO classification, based on morphology, molecular and immunophenotypic platforms. Results:ML cases increased steadily with each year from 2002 to 2011. Despite the introduction of an aggressive ART roll out program in 2004, HRL increased steadily from 4% in 2002 to 28% in 2011 with a profile of subtypes differing from the HIV negative cases. There is a predominance of Diffuse Large B Cell Lymphoma and Burkitt Lymphoma in the HIV positive cohort. The range of the CD4 count at presentation in a smaller cohort studied between 2010 and 2011 was from 20 to 620, with an average count of 150. Conclusion:These findings are in contrast to the observed pattern of reduced incidence of HRL in the developed world with the introduction of ART. This warrants evaluation in the manner and timing of introduction of ART in South Africa.