Angeliki Kerasidou

Reappraisal of known malaria resistance loci in a large multicenter study

Many human genetic associations with resistance to malaria have been reported, but few have been reliably replicated. We collected data on 11,890 cases of severe malaria due to Plasmodium falciparum and 17,441 controls from 12 locations in Africa, Asia and Oceania. We tested 55 SNPs in 27 loci previously reported to associate with severe malaria. There was evidence of association at P < 1 × 10−4 with the HBB, ABO, ATP2B4, G6PD and CD40LG loci, but previously reported associations at 22 other loci did not replicate in the multicenter analysis. The large sample size made it possible to identify authentic genetic effects that are heterogeneous across populations or phenotypes, with a striking example being the main African form of G6PD deficiency, which reduced the risk of cerebral malaria but increased the risk of severe malarial anemia. The finding that G6PD deficiency has opposing effects on different fatal complications of P. falciparum infection indicates that the evolutionary origins of this common human genetic disorder are more complex than previously supposed.

Consent and community engagement in diverse research contexts: reviewing and developing research and practice

Consent and community engagement (CE) in health research are two aspects of a single concern—that research is carried out in a respectful manner where social value is maximized. There are important overlaps and interdependencies between consent and CE; for example, CE can provide insights into how best to tailor consent to context and can be an important component of consent processes. Engaging communities can also have intrinsic and instrumental value beyond consent; for example, as a means of showing respect and identifying appropriate ways of working respectfully. In this paper we critically examine how CE and consent processes are characterized, conducted, and evaluated in diverse health research contexts, and propose a preliminary research agenda to support future learning in these critical areas.Consent and community engagement (CE) in health research are two aspects of a single concern-that research is carried out in a respectful manner where social value is maximized. There are important overlaps and interdependencies between consent and CE; for example, CE can provide insights into how best to tailor consent to context and can be an important component of consent processes. Engaging communities can also have intrinsic and instrumental value beyond consent; for example, as a means of showing respect and identifying appropriate ways of working respectfully. In this paper we critically examine how CE and consent processes are characterized, conducted, and evaluated in diverse health research contexts, and propose a preliminary research agenda to support future learning in these critical areas.

Making space for empathy: supporting doctors in the emotional labour of clinical care

BackgroundThe academic and medical literature highlights the positive effects of empathy for patient care. Yet, very little attention has been given to the impact of the requirement for empathy on the physicians themselves and on their emotional wellbeing.DiscussionThe medical profession requires doctors to be both clinically competent and empathetic towards the patients. In practice, accommodating both requirements can be difficult for physicians. The image of the technically skilful, rational, and emotionally detached doctor dominates the profession, and inhibits physicians from engaging emotionally with their patients and their own feelings, which forms the basis for empathy. This inhibition has a negative impact not only on the patients but also on the physicians. The expression of emotions in medical practice is perceived as unprofessional and many doctors learn to supress and ignore their feelings. When facing stressful situations, these physicians are more likely to suffer from depression and burnout than those who engage with and reflect on their feelings. Physicians should be supported in their emotional work, which will help them develop empathy. Methods could include questionnaires that aid self-reflection, and discussion groups with peers and supervisors on emotional experiences. Yet, in order for these methods to work, the negative image associated with the expression of emotions should be questioned. Also, the work conditions of physicians should improve to allow them to make use of these tools.SummaryEmpathy should not only be expected from doctors but should be actively promoted, assisted and cultivated in the medical profession.

Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection against Plasmodium falciparum malaria, but the precise nature of the protective effect has proved difficult to define as G6PD deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneous effects on the clinical outcome of P. falciparum infection. Here we report an analysis of multiple allelic forms of G6PD deficiency in a large multi-centre case-control study of severe malaria, using the WHO classification of G6PD mutations to estimate each individual’s level of enzyme activity from their genotype. Aggregated across all genotypes, we find that increasing levels of G6PD deficiency are associated with decreasing risk of cerebral malaria, but with increased risk of severe malarial anaemia. Models of balancing selection based on these findings indicate that an evolutionary trade-off between different clinical outcomes of P. falciparum infection could have been a major cause of the high levels of G6PD polymorphism seen in human populations. DOI: http://dx.doi.org/10.7554/eLife.15085.001

Trust me, I’m a researcher!: The role of trust in biomedical research

In biomedical research lack of trust is seen as a great threat that can severely jeopardise the whole biomedical research enterprise. Practices, such as informed consent, and also the administrative and regulatory oversight of research in the form of research ethics committees and Institutional Review Boards, are established to ensure the protection of future research subjects and, at the same time, restore public trust in biomedical research. Empirical research also testifies to the role of trust as one of the decisive factors in research participation and lack of trust as a barrier for consenting to research. However, what is often missing is a clear definition of trust. This paper seeks to address this gap. It starts with a conceptual analysis of the term trust. It compares trust with two other related terms, those of reliance and trustworthiness, and offers a defence of Baier’s attribute of ‘good will’ a basic characteristic of trust. It, then, proceeds to consider trust in the context of biomedical research by examining two questions: First, is trust necessary in biomedical research?; and second, do increases in regulatory oversight of biomedical research also increase trust in the field? This paper argues that regulatory oversight is important for increasing reliance in biomedical research, but it does not improve trust, which remains important for biomedical research. It finishes by pointing at professional integrity as a way of promoting trust and trustworthiness in this field.

Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

AbstractBackgroundMany studies report associations between human genetic factors and immunity to malaria but few have been reliably replicated. These studies are usually country-specific, use small sample sizes and are not directly comparable due to differences in methodologies. This study brings together samples and data collected from multiple sites across Africa and Asia to use standardized methods to look for consistent genetic effects on anti-malarial antibody levels.MethodsSera, DNA samples and clinical data were collected from 13,299 individuals from ten sites in Senegal, Mali, Burkina Faso, Sudan, Kenya, Tanzania, and Sri Lanka using standardized methods. DNA was extracted and typed for 202 Single Nucleotide Polymorphisms with known associations to malaria or antibody production, and antibody levels to four clinical grade malarial antigens [AMA1, MSP1, MSP2, and (NANP)4] plus total IgE were measured by ELISA techniques. Regression models were used to investigate the associations of clinical and genetic factors with antibody levels.ResultsMalaria infection increased levels of antibodies to malaria antigens and, as expected, stable predictors of anti-malarial antibody levels included age, seasonality, location, and ethnicity. Correlations between antibodies to blood-stage antigens AMA1, MSP1 and MSP2 were higher between themselves than with antibodies to the (NANP)4 epitope of the pre-erythrocytic circumsporozoite protein, while there was little or no correlation with total IgE levels. Individuals with sickle cell trait had significantly lower antibody levels to all blood-stage antigens, and recessive homozygotes for CD36 (rs321198) had significantly lower anti-malarial antibody levels to MSP2.ConclusionAlthough the most significant finding with a consistent effect across sites was for sickle cell trait, its effect is likely to be via reducing a microscopically positive parasitaemia rather than directly on antibody levels. However, this study does demonstrate a framework for the feasibility of combining data from sites with heterogeneous malaria transmission levels across Africa and Asia with which to explore genetic effects on anti-malarial immunity.

“You have to keep fighting”: maintaining healthcare services and professionalism on the frontline of austerity in Greece

BackgroundGreece has been severely affected by the 2008 global economic crisis and its health system was, and still is, among the national institutions most shaped by its effects.MethodsIn 2014, this qualitative study examined these changes through in-depth interviews with 22 frontline healthcare professionals in five different locations in mainland Greece. These interviews with nurses, doctors and pharmacists explored perceptions of austerity and how ideas of professionalism were challenged and revised by these measures.ResultsParticipants reported working conditions characterised by dramatic increases in public hospital admissions alongside decreases in personnel, consumables, materials, and also many hospital closures. Many drew on analogies of war and fighting to describe the effects of healthcare reforms on their working lives and professional conduct. Despite accounts of deteriorating conditions and numerous challenges, healthcare professionals presented themselves as making every effort to meet patients’ needs, while battling to resist guidelines which they perceived diminished their roles to production-line operatives.ConclusionsParticipants considered it their duty to defend their professional ethos and serve patients without compromising standards, even if this meant liberal interpretation and implementation of regulations. These professionals regarded themselves on the frontline of healthcare provision but also the frontline defence in a war on their professional standards from austerity.

Does science need bioethicists? Ethics and science collaboration in biomedical research

Biomedical research is an increasingly multidisciplinary activity bringing together a range of different academic fields and forms of expertise to investigate diseases that are increasingly understood to be complex and multifactorial. Recently the discipline of ethics has been starting to find a place in large-scale biomedical collaborations. In this article we draw from our experience of working with the Malaria Genomic Epidemiology Network (MalariaGEN) and other research projects to reflect upon the integration of ethics into biomedical research. We examine the way in which ethics input may be valuable to research, the forms it tends to take, and also the problems and limitations of such collaborations.

The Concept of Dignity and Its Use in End-of-Life Debates in England and France

Abstract: Dignity is one of the most controversial and yet commonly used terms in debates regarding end-of-life issues. The term “dignity” can take various meanings. For example, it can be used to denote the respect owed to an individual person, or to signify the intrinsic value of humankind as a whole. These two different understandings of dignity inevitably lead to different approaches to end-of-life decisionmaking. This article explores the meaning of the term “dignity” in two European countries, England and France. Our analysis compares public debates and legislation on end-of-life-related issues in these two countries. We argue that in England dignity is most commonly understood as respect for individual autonomy, whereas in France dignity usually signifies respect for humanity as a whole. We demonstrate that the difference in the conceptualization of the term leads to different ethical, and hence legal and practical, approaches to end-of-life issues and vulnerable patients. Our particular focus is on (1) withdrawing/withholding life-sustaining treatment, (2) respect for patient preferences, and (3) assistance in dying. Given the difference in the understanding of dignity, and the underlying philosophical approaches, it appears that there is still a long way to go before we can establish common guidelines on end-of-life decisions across Europe and beyond. However, clarifying the use of the term “dignity” in different discussions around Europe could hopefully facilitate this endeavor.

The value of sharing genomic findings with research ethics committees

The role of ethics committees is to protect and safeguard the rights and welfare of participants, and promote good research by providing ethical guidance to researchers. In order for ethics committees to fulfil their role and obligations, they need to have adequate understanding of the science and scientific methods used in research. Genomics is a novel and rapidly evolving research field, and identifying the ethical issues raised by it is not straightforward. Limited understanding of, and expertise in, reviewing genomic research may lead ethics committees to either hamper novel research, or overlook important ethical problems. Researchers are in the best position to assist ethics committees in their efforts to remain informed about scientific advancements.