Anti-merozoite antibodies induce natural killer cell effector function and are associated with immunity against malaria.

Natural killer (NK) cells are potent immune effectors that can be activated via antibody-mediated Fc receptor engagement. Using multiparameter flow cytometry, we found that NK cells degranulate and release IFN-γ upon stimulation with antibody-opsonized Plasmodium falciparum merozoites. Antibody-dependent NK (Ab-NK) activity was largely strain transcending and enhanced invasion inhibition into erythrocytes. Ab-NK was associated with the successful control of parasitemia after experimental malaria challenge in African adults. In an independent cohort study in children, Ab-NK increased with age, was boosted by concurrent P. falciparum infections, and was associated with a lower risk of clinical episodes of malaria. Nine of the 14 vaccine candidates tested induced Ab-NK, including some less well-characterized antigens: P41, P113, MSP11, RHOPH3, and Pf_11363200. These data highlight an important role of Ab-NK activity in immunity against malaria and provide a potential mechanism for evaluating vaccine candidates.

Ethical Considerations for Movement Mapping to Identify Disease Transmission Hotspots.

Traditional public health methods for detecting infectious disease transmission, such as contact tracing and molecular epidemiology, are time-consuming and costly. Information and communication technologies, such as global positioning systems, smartphones, and mobile phones, offer opportunities for novel approaches to identifying transmission hotspots. However, mapping the movements of potentially infected persons comes with ethical challenges. During an interdisciplinary meeting of researchers, ethicists, data security specialists, information and communication technology experts, epidemiologists, microbiologists, and others, we arrived at suggestions to mitigate the ethical concerns of movement mapping. These suggestions include a template Data Protection Impact Assessment that follows European Union General Data Protection Regulations.

Kenyan health stakeholder views on individual consent, general notification and governance processes for the re-use of hospital inpatient data to support learning on healthcare systems.

BACKGROUND: Increasing adoption of electronic health records in hospitals provides new opportunities for patient data to support public health advances. Such learning healthcare models have generated ethical debate in high-income countries, including on the role of patient and public consent and engagement. Increasing use of electronic health records in low-middle income countries offers important potential to fast-track healthcare improvements in these settings, where a disproportionate burden of global morbidity occurs. Core ethical issues have been raised around the role and form of information sharing processes for learning healthcare systems, including individual consent and individual and public general notification processes, but little research has focused on this perspective in low-middle income countries. METHODS: We conducted a qualitative study on the role of information sharing and governance processes for inpatient data re-use, using in-depth interviews with 34 health stakeholders at two public hospitals on the Kenyan coast, including health managers, providers and researchers. Data were collected between March and July 2016 and analysed using a framework approach, with Nvivo 10 software to support data management. RESULTS: Most forms of clinical data re-use were seen as an important public health good. Individual consent and general notification processes were often argued as important, but contingent on interrelated influences of the type of data, use and secondary user. Underlying concerns were linked to issues of patient privacy and autonomy; perceived risks to trust in health systems; and fairness in how data would be used, particularly for non-public sector re-users. Support for engagement often turned on the anticipated outcomes of information-sharing processes, as building or undermining trust in healthcare systems. CONCLUSIONS: As reported in high income countries, learning healthcare systems in low-middle counties may generate a core ethical tension between supporting a public good and respecting patient autonomy and privacy, with the maintenance of public trust acting as a core requirement. While more evidence is needed on patient and public perspectives on learning healthcare activities, greater collaboration between public health and research governance systems is likely to support the development of efficient and locally responsive learning healthcare activities in LMICs.

Ethical considerations in Controlled Human Malaria Infection studies in low resource settings: Experiences and perceptions of study participants in a malaria Challenge study in Kenya.

Background: The range and amount of volunteer infection studies, known as Controlled Human Infection Model (CHMI) studies, in Low-Middle Income Countries (LMICs) is increasing with rapid technological advancement, world-class laboratory facilities and increasing capacity development initiatives. However, the ethical issues these studies present in LMICs have not been empirically studied. We present findings of a descriptive social science study nested within a malaria volunteer infection study, on-going at the time of writing, at the KEMRI-Wellcome Trust Research Programme (KWTRP) on the Kenyan Coast. Methods: The study included non-participant observations, five group discussions with more than half of the CHMI study participants, two in-depth interviews with study team members, and an exit questionnaire administered to the participants. Results: Participants understood the key elements of the study, including that they would be deliberately infected with malaria parasites and may get malaria as a result, there would be regular blood draws, and they would spend up to 24 days in a residence facility away from their homes. The greatest motivation for participation was the monetary compensation of 20 USD per overnight stay given as a lump-sum at the end of their residency stay. Also appreciated were the health screening tests prior to enrolment and the positive relations with the study team. Concerns raised included the amount and regularity of blood draws experienced, and concerns that this type of research may feed into on-going rumours about research generally. Conclusion: With the increasing range and number of CHMI studies being conducted in LMICs, current ethical guidance are inadequate.  This study highlights some of the ethical issues that could emerge in these settings, emphasizing the heavy responsibility placed on research review and regulatory systems, researchers and funders, as well as the importance of carefully tailored community engagement and consent processes.

Benefits in cash or in kind? A community consultation on types of benefits in health research on the Kenyan Coast.

BACKGROUND: Providing benefits and payments to participants in health research, either in cash or in kind, is a common but ethically controversial practice. While much literature has concentrated on appropriate levels of benefits or payments, this paper focuses on less well explored ethical issues around the nature of study benefits, drawing on views of community members living close to an international health research centre in Kenya. METHODS: The consultation, including 90 residents purposively chosen to reflect diversity, used a two-stage deliberative process. Five half-day workshops were each followed by between two and four small group discussions, within a two week period (total 16 groups). During workshops and small groups, facilitators used participatory methods to share information, and promote reflection and debate on ethical issues around types of benefits, including cash, goods, medical and community benefits. Data from workshop and field notes, and voice recordings of small group discussions, were managed using Nvivo 10 and analysed using a Framework Analysis approach. FINDINGS AND CONCLUSIONS: The methods generated in-depth discussion with high levels of engagement. Particularly for the most-poor, under-compensation of time in research carries risks of serious harm. Cash payments may best support compensation of costs experienced; while highly valued, goods and medical benefits may be more appropriate as an 'appreciation' or incentive for participation. Community benefits were seen as important in supporting but not replacing individual-level benefits, and in building trust in researcher-community relations. Cash payments were seen to have higher risks of undue inducement, commercialising relationships and generating family conflicts than other benefits, particularly where payments are high. Researchers should consider and account for burdens families may experience when children are involved in research. Careful context-specific research planning and skilled and consistent communication about study benefits and payments are important, including in mitigating potential negative effects.

What are fair study benefits in international health research? Consulting community members in Kenya.

BACKGROUND: Planning study benefits and payments for participants in international health research in low- income settings can be a difficult and controversial process, with particular challenges in balancing risks of undue inducement and exploitation and understanding how researchers should take account of background inequities. At an international health research programme in Kenya, this study aimed to map local residents' informed and reasoned views on the effects of different levels of study benefits and payments to inform local policy and wider debates in international research. METHODS AND FINDINGS: Using a relatively novel two-stage process community consultation approach, five participatory workshops involving 90 local residents from diverse constituencies were followed by 15 small group discussions, with components of information-sharing, deliberation and reflection to situate normative reasoning within debates. Framework Analysis drew inductively and deductively on voice-recorded discussions and field notes supported by Nvivo 10 software, and the international research ethics literature. Community members' views on study benefits and payments were diverse, with complex contextual influences and interplay between risks of giving 'too many' and 'too few' benefits, including the role of cash. While recognising important risks for free choice, research relationships and community values in giving 'too many', the greatest concerns were risks of unfairness in giving 'too few' benefits, given difficulties in assessing indirect costs of participation and the serious consequences for families of underestimation, related to perceptions of researchers' responsibilities. CONCLUSIONS: Providing benefits and payments to participants in international research in low-income settings is an essential means by which researchers meet individual-level and structural forms of ethical responsibilities, but understanding how this can be achieved requires a careful account of social realities and local judgment. Concerns about undue inducement in low-income communities may often be misplaced; we argue that greater attention should be placed on avoiding unfairness, particularly for the most-poor.

'The words will pass with the blowing wind': staff and parent views of the deferred consent process, with prior assent, used in an emergency fluids trial in two African hospitals.

OBJECTIVE: To document and explore the views and experiences of key stakeholders regarding the consent procedures of an emergency research clinical trial examining immediate fluid resuscitation strategies, and to discuss the implications for similar trials in future. METHODS: A social science sub-study of the FEAST (Fluid Expansion As Supportive Therapy) trial. Interviews were held with trial team members (n = 30), health workers (n = 15) and parents (n = 51) from two purposively selected hospitals in Soroti, Uganda, and Kilifi, Kenya. FINDINGS: Overall, deferred consent with prior assent was seen by staff and parents as having the potential to protect the interests of both patients and researchers, and to avoid delays in starting treatment. An important challenge is that the validity of verbal assent is undermined when inadequate initial information is poorly understood. This concern needs to be balanced against the possibility that full prior consent on admission potentially causes harm through introducing delays. Full prior consent also potentially imposes worries on parents that clinicians are uncertain about how to proceed and that clinicians want to absolve themselves of any responsibility for the child's outcome (some parents' interpretation of the need for signed consent). Voluntariness is clearly compromised for both verbal assent and full prior consent in a context of such vulnerability and stress. Further challenges in obtaining verbal assent were: what to do in the absence of the household decision-maker (often the father); and how medical staff handle parents not giving a clear agreement or refusal. CONCLUSION: While the challenges identified are faced in all research in low-income settings, they are magnified for emergency trials by the urgency of decision making and treatment needs. Consent options will need to be tailored to particular studies and settings, and might best be informed by consultation with staff members and community representatives using a deliberative approach.